Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.Thi...Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.This study featured the combined supplementation of soy lecithin(SL)and soy isoflavones(SIF),using in vivo animal models,in vitro vascular ring preparation,and cell studies to investigate the potential advantages and mechanisms of SL combined with SIF on cognitive function and cerebrovascular health from multiple perspectives.The results show that Aβcan significantly induce learning and memory impairment in rats,as well as pathological changes in brain blood vessels,exacerbating damage to cerebral vasodilation function and subsequently reducing cerebral blood flow in the brain.The above-mentioned phenomena induced by Aβcan be significantly improved by the combined intervention of SL and SIF.Further research has revealed that the combined intervention of SL and SIF can reverse the downregulation of the PI3K/PIP3/PDK-1/Akt/eNOS signaling pathway and phosphorylated protein expression induced by Aβin rat brain vascular tissues and bEND.3 cells.Silencing PDK-1 expression in bEND.3 cells showed that the upregulation effect of SL and SIF on Akt and eNOS disappeared.Here we find that prophylactically supplementation with SL in conjunction with SIF appears to effectively activate the PI3K/PIP3/PDK-1/Akt/e NOS pathway within cerebral vascular.This activation improves cerebrovascular vasodilation,offering potential protective effects for both cerebral vascular health and cognitive function.展开更多
In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-ind...In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-induced platelet aggregation.The present paper revealed that RG- DS had vasodilative action and the cGMP accumulation may be one of the mechanisms of RGDS exer- ting bioactivities.展开更多
In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, m...In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.展开更多
AIM:To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP...AIM:To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP-90 were analyzed by immunofluorescence, western blotting and co-immunoprecipitation in the mesenteric vasculature and isolated nerves of portal-vein-ligated (PVL) rats and sham operated rats. In vitro perfused de-endothelialized mesenteric arterial vasculature was preconstricted with norepinephrine (EC80) and tested for nNOS-mediated vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45V) before and after incubation with geldanamycin (specific inhibitor of HSP-90 signalling, 3 μg/mL) or L-NAME (non-specific NOSblocker, 10-4 mol/L). RESULTS: nNOS and HSP-90 expression was significantly increased in mesenteric nerves from PVL as compared to sham rats. Moreover, nNOS and HSP-90 were visualized in mesenteric nerves by immunofluorescence and immunoprecipitation of nNOS co-immunoprecitated HSP-90 in sham and PVL rats. PNS induced a frequencydependent vasorelaxation which was more pronounced in PVL as compared to sham rats. L-NAME and geldanamycin markedly reduced nNOS-mediated vasorelaxation abrogating differences between the study groups. The effect of L-NAME and geldanamycin on nNOS-mediated vasorelaxation was significantly greater in PVL than in sham animals. However, no difference in magnitude of effect between L-NAME and geldanamycin was noted. CONCLUSION: HSP-90 acts as a signalling mediator of nNOS-dependent nerve mediated vascular responses in mesenteric arteries, and the increased nitrergic vasorelaxation observed in portal hypertension is mediated largely by HSP-90.展开更多
Background: The magnitude of the hyperemic response due to repeated thigh stump exercise on incremental contraction intensity might be useful information in localized exercise tolerance for devising cardiovascular phy...Background: The magnitude of the hyperemic response due to repeated thigh stump exercise on incremental contraction intensity might be useful information in localized exercise tolerance for devising cardiovascular physical therapy for amputees. The effect of exercise on amputated leg blood flow (LBF) may potentially be altered due to voluntary muscle contractions after loss of the lower leg compared with the healthy leg. Case Presentation: A 57-year-old male patient with Burger disease attempted 3 min unilateral repeat/dynamic knee extensor exercise at a target muscle contraction frequency (1 s thigh muscle contraction and 1 s relaxation, 90 repetitions) with each leg <right transtibial amputated leg (AL) using a total surface-bearing prosthesis (TSB) and left non-AL> at six different contraction intensities (rubber resistance belt). Simultaneous measurement of blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, leg vascular conductance (LVC), and peak muscle strength (PMS) were performed during the 3 min exercise period. The maximum voluntary contraction by one-legged isometric knee muscle contraction was 14.7 kg in non-AL and 7.9 kg in the AL with prosthesis. The relative PMS was defined as “PMS/maximum voluntary contraction × 100 (%)”. Pre-exercise LBF was lower in the AL (200 ± 25 ml/min) than the non-AL (275 ± 74 ml/min). Both the non-AL and AL showed good positive linear relationships between absolute-/relative-PMS and LBF or LVC during 30 s at steady-state before the end of the exercise period. Furthermore, there was also similarity seen in the increase rate in LBF and/or LVC for the incremental relative PMS compared with the absolute PMS. Conclusion: In this case, the muscle strength depended on blood flow increase/vasodilation was seen in this “AL” using a TSB prosthesis for repeated dynamic knee extensor exercise. The present amputee’s limb muscle strengthening with the resection stump closely related to the degree of hyperemia in the amputated limb.展开更多
In this study,Ulva prolifera protein was used for preparing angiotensin-I converting enzyme(ACE)-inhibitory peptide via virtual gastrointestinal digestion and in silico screening.Some parameters of the obtained peptid...In this study,Ulva prolifera protein was used for preparing angiotensin-I converting enzyme(ACE)-inhibitory peptide via virtual gastrointestinal digestion and in silico screening.Some parameters of the obtained peptide,such as inhibition kinetics,docking mechanism,stability,transport pathway,were explored by Lineweaver-Burk plots,molecular docking,in vitro stimulate gastrointestinal(GI)digestion and Caco-2 cells monolayer model,respectively.Then,a novel anti-ACE peptide LDF(IC_(50),(1.66±0.34)μmol/L)was screened and synthesized by chemical synthesis.It was a no-competitive inhibitor and its anti-ACE inhibitory effect mainly attributable to four Conventional Hydrogen Bonds and Zn701 interactions.It could keep activity during simulated GI digestion in vitro and was transported by peptide transporter PepT1 and passive-mediated mode.Besides,it could activate Endothelial nitric oxide synthase(eNOS)activity to promote the production of NO and reduce Endothelin-1(ET-1)secretion induced by AngiotensinⅡ(AngⅡ)in Human Umbilical Vein Endothelial Cells(HUVECs).Meanwhile,it could promote mice splenocytes proliferation in a concentration-dependent manner.Our study indicated that this peptide was a potential ingredient functioning on vasodilation and enhancing immunity.展开更多
The binding of Fgn to GPIIb / IIIa has confirmed that there are two distinct amino acid sequences within the Fgn molecule that are responsible for mediating its attachment to GP IIb / IIIa receptor. In addition to mon...The binding of Fgn to GPIIb / IIIa has confirmed that there are two distinct amino acid sequences within the Fgn molecule that are responsible for mediating its attachment to GP IIb / IIIa receptor. In addition to monoclonal antibodies, the binding function of GP IIb / IIIa can be blocked by synthetic small peptides containing the RGD and APLRV sequence. In our preliminary study it was found that besides inhibition of platelet aggregation and thrombus formation RGDS showed vasodilation effects as well. In an attempt to confirm the vasodilation effect of RGDS related peptides, RGDF, APLRV, APLRVRGDS and APLRVRGDF were investigated. The effects of these synthetic peptides on rat aortic strips pretreated with NE in vitro were observed. The relaxing extents of contracted strips for the peptides at three doses (10 5 mol / L, 10 6 mol / L and 10 7 mol / L) were recorded.展开更多
Background: The production of endothelial-derived factors induces either vasoconstriction or vasodilation;nitric oxide (NO) is the most distinguished relaxing factor. Endothelial dysfunction is associated with hyperte...Background: The production of endothelial-derived factors induces either vasoconstriction or vasodilation;nitric oxide (NO) is the most distinguished relaxing factor. Endothelial dysfunction is associated with hypertension. The partial loss in the NO-promoted vasodilation is due to its decreased bioavailability and/or to an activity reduction of endothelium NO synthase (eNOS). Reactive oxygen species (ROS), present in oxidative stress, seize NO and diminish its bioavailability. Transresveratrol (RESV) has been proved to increase NO and eNOS levels. Thus, RESV could be capable of improving NO dependent vascular relaxation on aortic rings isolated from treated 2K-1C animals through ROS damage reduction. Aim: Evaluate the effects of RESV treatment on the relaxation of aortic rings isolated from treated 2K-1C rats while focusing on the effects of the treatment on systolic blood pressure. Methods: Male Wistar rats (180 g) were grouped: two 2K-1C and two Sham groups, one of each was treated with RESV (20 mg/kg, gavage) dissolved in Tween 80 and one of each was treated with water plus Tween 80 (control) for six weeks. The rats had their systolic blood pressure (SBP) measured before and after the treatments. Vascular reactivity studies were conducted in order to observe and compare acetylcholine (ACh)-induced relaxations in the presence and absence of the NOS inhibitor L-NAME (10-4 mol/L). Results: SBP for 2K-1C was significantly reduced in the treated group (179.13 ± 4.90 mmHg, n = 23) when compared to the untreated group (196.66 ± 6.06 mmHg, n = 15, p < 0.01). The maximum relaxation of aortic rings isolated from the 2K-1C treated group showed a higher efficacy (116.63% ± 1.72%, n = 12) than that from the untreated group (85.97% ± 0.69%, n = 6, p < 0.001);L-NAME exposure was responsible for a significant decrease in each group’s maximum relaxation efficacy. Conclusions: SBP reduction observed after RESV treatment in rat renal hypertension could be due to the reestablishment of vascular relaxation depend of NO.展开更多
Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic ...Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic acid,tanshinol,and hydroxysafflor yellow A(FTA)in GXⅡ/rat serum after the oral administration of GXⅡ(30 g/kg)were detected using ultra-performance liquid chromatography-mass spectrometry.Totally 18 rats were randomly assigned to the control group(0.9%normal saline),GXⅡ(30 g/kg)and FTA(5,28 and 77 mg/kg)by random number table method.Diastolic coronary flow velocity-time integral(VTI),i.e.,coronary flow or coronary flow-mediated dilation(CFMD),and endothelium-intact vascular tension of isolated aortic rings were measured.After 12 h of exposure to blank medium or 0.5 mmol/L H_(2)O_(2),endothelial cells(ECs)were treated with post-dose GXⅡof supernatant from deproteinized serum(PGSDS,300μL PGSDS per 1 m L of culture medium)or FTA(237,1539,and 1510 mg/m L)for 10 min as control,H_(2)O_(2),PGSDS and FTA groups.Nitric oxide(NO),vascular endothelial growth factor(VEGF),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA)and phosphorylated phosphoinositide 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),phosphorylated endothelial nitric oxide synthase(p-e NOS)were analyzed.PGSDS was developed as a GXⅡproxy of ex vivo herbal crude extracts.Results:PGSDS effectively eliminates false responses caused by crude GXⅡpreparations.When doses equaled the contents in GXⅡ/its post-dose serum,FTA accounted for 98.17%of GXⅡ-added CFMD and 92.99%of PGSDS-reduced vascular tension.In ECs,FTA/PGSDS was found to have significant antioxidant(lower MDA and higher SOD,P<0.01)and endothelial function-protective(lower VEGF,ET-1,P<0.01)effects.The increases in aortic relaxation,endothelial NO levels and phosphorylated PI3K/Akt/e NOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester(L-NA,e NOS inhibitor)and wortmannin(PI3K/AKT inhibitor),respectively,indicating an endothelium-dependent vasodilation via the PI3K/AKT-e NOS pathway(P<0.01).Conclusion:This study provides a strategy for rapidly and precisely elucidating GXⅡ's representative in/ex vivo cardioprotective absorbed bioactive compounds(ABCs)-FTA,suggesting its potential in advancing precision ethnomedicine.展开更多
Objective: To explore the effect of Kuanxiong Aerosol(KXA)on isoproterenol(ISO)-induced myocardial injury in rat models.Methods: Totally 24 rats were radomly divided into control,ISO,KXA low-dose and high-dose groups ...Objective: To explore the effect of Kuanxiong Aerosol(KXA)on isoproterenol(ISO)-induced myocardial injury in rat models.Methods: Totally 24 rats were radomly divided into control,ISO,KXA low-dose and high-dose groups according to the randomized block design method,and were administered by intragastric administration for 10 consecutive days,and on the 9th and 10th days,rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA.In addition,the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test.The influence of KXA on the expression of calcium-CaM-dependent protein kinase Ⅱ(CaMK Ⅱ)/extracellular regulated protein kinases(ERK)signaling pathway has also been tested.Results: KXA significantly reduced the ISO-induced increase in ST-segment,interventricular septal thickness,cardiac mass index and cardiac tissue pathological changes in rats.Moreover,the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine(NE)or potassium chloride(KCl)was increased after KXA treatment in an endothelium-independent manner,and was attenuated by preincubation with verapamil,but not with tetraethylammonium chloride,4-aminopyridine,glibenclamide,or barium chloride.KXA pretreatment attenuated vasoconstriction induced by CaCl_(2)in Ca^(2+)-free solutions containing K^(+) or NE.In addition,KXA pretreatment inhibited accumulation of Ca^(2+)in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK Ⅱ and p-ERK levels.Conclusion: KXA may inhibit influx and release of calcium and activate the CaMK Ⅱ/ERK signaling pathway to produce vasodilatory effects,thereby improving myocardial injury.展开更多
Normal pregnancy is associated with dramatically increased estrogen biosynthesis whose role is believed to raise uterine blood flow to facilitate the bi-directional maternal-fetal exchanges of gases(O_(2) and CO_(2)),...Normal pregnancy is associated with dramatically increased estrogen biosynthesis whose role is believed to raise uterine blood flow to facilitate the bi-directional maternal-fetal exchanges of gases(O_(2) and CO_(2)),to deliver nutrients,and exhaust wastes to support fetal development and survival.Constrained uterine blood flow in pregnancy is a leading cause of preeclampsia with fetal growth restriction,rendering investigations of uterine hemodynamics to hold a high promise to inform pathways as targets for therapeutic interventions for preeclampsia.The mechanisms of estrogen-induced uterine vasodilation in pregnancy have long been attributed to enhanced endothelium production of nitric oxide,but clinical trials targeting this pathway that dominates uterine hemodynamics have achieved no to little success.Emerging evidence has recently shown a novel proangiogenic vasodilatory role of hydrogen sulfide in regulating uterine hemodynamics in pregnancy and preeclampsia,provoking a new field of perinatal research in searching for alternative pathways for pregnancy disorders especially preeclampsia and intrauterine growth restriction.This minireview is intended to summarize the nitric oxide pathway and to discuss the emerging hydrogen sulfide pathway in modulating estrogen-induced uterine vasodilation in pregnancy and preeclampsia.展开更多
Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function i...Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study. Methods In the prospective study, we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years. Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia and obesity. We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay, endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound. At year 8, 102 patients were reexamined for endothelium-dependent and -independent vasodilation. Results Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline （r=0.150, P=0.043） and at year 8 （r=0.339, P=0.001）, whereas no association was found between adiponectin and endothelium-dependent vasodilation. In a stepwise multivariate linear regression model, adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 （P=0.001）. Conclusions Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention. These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.展开更多
Objectives To investigate whether lovastatin improves endothelium dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals, as compared with L arginine. Methods Forty male rabbits, rando...Objectives To investigate whether lovastatin improves endothelium dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals, as compared with L arginine. Methods Forty male rabbits, randomized into four groups with ten in each group, were fed with one of the following diets: ① normal rabbit chow; ② 1% cholesterol diet; ③ 1% cholesterol diet supplemented with 2.25 g/kg L arginine soluble in the physiological salt solution (PPS) by gavage; ④ 1% cholesterol diet supplemented with 10 mg/kg lovastatin soluble in the PSS by gavage. The rabbits were fed with these diets for 10 weeks, and blood samples were collected from animals for biochemical studies. Then aortic rings were obtained, and changes in isometric tension were recorded. Intimal atherosclerotic areas of the aortae were subsequently measured by planimetry. Results Serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL C) levels were lower￣ ed (30%±6%, 39%±4%, respectively) and high Department of Cardiovascular Internal Medicine, First Affiliated Hospital, Henan Medical University, Zhengzhou 450052, China (Zhang JY, Dong JZ, Li L, Zhao LS, Huang ZW, Wei JH and Liu RY) This work was supported by the Education Committee of Henan Province, China, and a grant from the Henan Science and Technology Committee. density lipoprotein cholesterol (HDL C) elevated (11%±3%) in the rabbits receiving 1% cholesterol diet supplemented with lovastatin, compared with those (including TC, LDL C, and HDL C) in the rabbits receiving 1% cholesterol diet and 1% cholesterol diet supplemented with L arginine, with alteration to the same degree. Endothelium dependent relaxations to acetylcholine were significantly impaired in aortae from the animals fed with a 1% cholesterol diet. By contrast, vessels from the hypercholesterolemic animals both receiving L arginine and lovastatin supplementation revealed significantly improved endothelium dependent relaxations. In addition, vessels from the hypercholesterolemic animals receiving L arginine were superior to those from those receiving lovastatin. Histomorphometric analysis showed a reduction in lesion surface area in aortae from the arginine and lovastatin supplemented animals compared to those from untreated hypercholesterolemic rabbits, moreover, lesion surface areas in aortae from both the arginine and lovastatin supplemented animals were similar (P>0.05). Conclusions This study demonstrates that lovastatin could improve endothelium dependent vasorelaxation. By contrast, L arginine is superior to lovastatin, but a reduced surface area in aortae is not different between the two drugs.展开更多
Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to ...Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to induce coronary vasospasm remains largely underreported.[1]Minoxidil is currently reserved for treating alopecia for various causes.展开更多
BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral an...BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral and non-viral etiologies are treated by traditional ARDS protocols that recommend 12-16 hours of prone position ventilation(PPV)with neuromuscular blocking agents(NMBA)and a trial of inhaled vasodilators(IVd)if oxygenation does not improve.However,debate on the efficacy of adjuncts to PPV and low tidal volume ventilation persists and evidence about the benefits of IVd/NMBA in COVID ARDS is sparse.In our multi-center retrospective review,we evaluated the impact of PPV,IVd,and NMBA on outcomes and lung mechanics in COVID ARDS patients with moderate to severe ARDS.AIM To evaluate the impact of PPV used alone or in combination with pulmonary IVd and/or NMBA in mechanically ventilated patients with moderate to severe ARDS during the COVID-19 pandemic.METHODS A retrospective study at two tertiary academic medical centers compared outcomes between COVID ARDS patients receiving PPV and patients in the supine position.PPV patients were divided based on concurrent use of ARDS adjunct therapies resulting in four subgroups:(1)PPV alone;(2)PPV and IVd;(3)PPV and NMBA;and(4)PPV,IVd,and NMBA.Primary outcomes were hospital and intensive care unit(ICU)length of stay(LOS),mortality,and venovenous extracorporeal membrane oxygenation(VV-ECMO)status.Secondary outcomes included changes in lung mechanics at 24-hour intervals for 7 days.RESULTS Total 114 patients were included in this study.Baseline respiratory parameters and Sequential Organ Failure Assessment scores were significantly worse in the PPV group.ICU LOS and LOS were significantly longer for patients who were proned,but no mortality benefit or difference in VV-ECMO status was found.Among the subgroups,no difference in primary outcomes were found.In the secondary analysis,PPV was associated with a significant improvement in arterial oxygen partial pressure(PaO_(2))/fractional inspired oxygen(FiO_(2))(P/F)ratio from day 1 to day 4(P<0.05)and higher driving pressures day 5 to day 7(P<0.05).The combination of PPV and IVd together resulted in improvements in P/F ratio from day 1 to day 7 and plateau pressure on day 4 and day 6(P<0.05).PPV with NMBA was not associated with improvements in any of the secondary outcomes.The use of all three rescue therapies together resulted in improvements in lung compliance on day 2(P<0.05)but no other improvements.CONCLUSION In mechanically ventilated patients diagnosed with moderate to severe COVID ARDS,PPV and PPV with the addition of IVd produced a significant and sustained increase in P/F ratio.The combination of PPV,IVd and NMBA improved compliance however this did not reach significance.Mortality and LOS did not improve with adjunct therapies.Further research is warranted to determine the efficacy of these therapies alone and in combination in the treatment of COVID ARDS.展开更多
Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s ame...Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s amelioration of ischaemic stroke and its effective constituents remain unclear. The present study aimed to identify the effective constituents of BYHWD and to further explore its action mechanisms in the amelioration of ischaemic stroke by testing the activities of 15 absorbable chemical constituents of BYHWD with the same methods under the same conditions. The following actions of these 15 compounds were revealed： 1） Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-β-D-glucoside, paeonol, calycosin-7-O-β-D-glucoside, astraisofla- van-7-O-β-D-glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin A （Con A）-induced T lymphocyte proliferation; 2） Propyl gallate, calycosin-7-O-β-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced apoptosis in RAW264.7 cells; 3） Propyl gallate and formononetin significantly inhibited LPS-induced NO release; 4） Hydroxysaffior yellow A and inosine protected PC12 cells against the injuries caused by glutamate; and 5） Formononetin, astragaloside IV, astraisofiavan-7-O-β-D- glucoside, inosine, paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid significantly suppressed the constriction of the thoracic aorta induced by KCI in rats. In conclusion, the results from the present study suggest that BYHWD exerts its ischaemic stroke ameliorating activities by modulating multiple targets with multiple components.展开更多
Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expa...Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.展开更多
Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we...Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction(ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate(c GMP) dependent protein kinase(PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and-independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU(10–1 000 μmol·L-1) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-c GMPS(PKGI-rp, 4 μmol·L-1), significantly blocked SCU(10–1 000 μmol·L-1)-induced relaxation. The NO synthase(NOS) inhibitor, NO-nitro-L-arginine methylester(L-NAME, 100 μmol·L-1), did not significantly change the effects of SCU(10–1 000 μmol·L-1). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU(500 μmol·L-1), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp(4 μmol·L-1) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein(p-VASP,phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.展开更多
AIM:Adrenomedullin (ADM) is a potent vasodilator peptide. ADM and nitric oxide (NO) are produced in vascular endothelial cells.Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatatio...AIM:Adrenomedullin (ADM) is a potent vasodilator peptide. ADM and nitric oxide (NO) are produced in vascular endothelial cells.Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH).The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown,plasma ADM levels were studied in patients with NCPH,compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups. METHODS:There were 4 groups of subjects.Group 1 consisted of 27 patients (F/M:12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age:41±12 years),group 2 consisted of 14 patients (F/M:6/8) with compensated (Child-Pugh A) cirrhosis (mean age:46±4), group 3 consisted of 16 patients (F/M:6/10) with decompensated (Child-Pugh C) cirrhosis (mean age:47±12). Fourteen healthy subjects (F/M:6/8) (mean age:44±8) were used as controls in Group 4.ADM level was measured by ELISA.NO was determined as nitrite/nitrate level by chemoluminescence. RESULTS:ADM level in Group 1 (236±61.4 pg/mL) was significantly higher than that in group 2 (108.4±28.3 pg/mL) and group 4 (84.1±31.5 pg/mL) (both P<0.0001) but was lower than that in Group3 (324±93.7 pg/mL) (P=0.002).NO level in group 1 (27±1.4 μmol/L) was significantly higher than that in group 2 (19.8±2.8 μmol/L) and group 4 (16.9±1.6 μmol/L) but was lower than that in Group 3 (39±3.6 μmol/L) (for all three P<0.0001).A strong correlation was observed between ADM and NO levels (r=0.827,P<0.0001). CONCLUSION:Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated,Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis,and were significantly higher than those in patients with NCPH. Portal hypertension plays an important role in the increase of ADM and NO.Parenchymal damage in cirrhosis may contribute to the increase in these parameters.展开更多
Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a...Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.展开更多
基金supported by the National Natural Science Foundation of China(82273620,81302427)。
文摘Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.This study featured the combined supplementation of soy lecithin(SL)and soy isoflavones(SIF),using in vivo animal models,in vitro vascular ring preparation,and cell studies to investigate the potential advantages and mechanisms of SL combined with SIF on cognitive function and cerebrovascular health from multiple perspectives.The results show that Aβcan significantly induce learning and memory impairment in rats,as well as pathological changes in brain blood vessels,exacerbating damage to cerebral vasodilation function and subsequently reducing cerebral blood flow in the brain.The above-mentioned phenomena induced by Aβcan be significantly improved by the combined intervention of SL and SIF.Further research has revealed that the combined intervention of SL and SIF can reverse the downregulation of the PI3K/PIP3/PDK-1/Akt/eNOS signaling pathway and phosphorylated protein expression induced by Aβin rat brain vascular tissues and bEND.3 cells.Silencing PDK-1 expression in bEND.3 cells showed that the upregulation effect of SL and SIF on Akt and eNOS disappeared.Here we find that prophylactically supplementation with SL in conjunction with SIF appears to effectively activate the PI3K/PIP3/PDK-1/Akt/e NOS pathway within cerebral vascular.This activation improves cerebrovascular vasodilation,offering potential protective effects for both cerebral vascular health and cognitive function.
基金This project was supported by the National Natural Science Foundation
文摘In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-induced platelet aggregation.The present paper revealed that RG- DS had vasodilative action and the cGMP accumulation may be one of the mechanisms of RGDS exer- ting bioactivities.
基金Supported by the Grants from the Ministerio de Educacióny Ciencia, No. SAF2006-0314the Ministerio de Cienciae Innovación, No. SAF2009-08354
文摘In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.
基金Supported by Grants from the German Research Association (DFG) to Wiest R
文摘AIM:To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP-90 were analyzed by immunofluorescence, western blotting and co-immunoprecipitation in the mesenteric vasculature and isolated nerves of portal-vein-ligated (PVL) rats and sham operated rats. In vitro perfused de-endothelialized mesenteric arterial vasculature was preconstricted with norepinephrine (EC80) and tested for nNOS-mediated vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45V) before and after incubation with geldanamycin (specific inhibitor of HSP-90 signalling, 3 μg/mL) or L-NAME (non-specific NOSblocker, 10-4 mol/L). RESULTS: nNOS and HSP-90 expression was significantly increased in mesenteric nerves from PVL as compared to sham rats. Moreover, nNOS and HSP-90 were visualized in mesenteric nerves by immunofluorescence and immunoprecipitation of nNOS co-immunoprecitated HSP-90 in sham and PVL rats. PNS induced a frequencydependent vasorelaxation which was more pronounced in PVL as compared to sham rats. L-NAME and geldanamycin markedly reduced nNOS-mediated vasorelaxation abrogating differences between the study groups. The effect of L-NAME and geldanamycin on nNOS-mediated vasorelaxation was significantly greater in PVL than in sham animals. However, no difference in magnitude of effect between L-NAME and geldanamycin was noted. CONCLUSION: HSP-90 acts as a signalling mediator of nNOS-dependent nerve mediated vascular responses in mesenteric arteries, and the increased nitrergic vasorelaxation observed in portal hypertension is mediated largely by HSP-90.
文摘Background: The magnitude of the hyperemic response due to repeated thigh stump exercise on incremental contraction intensity might be useful information in localized exercise tolerance for devising cardiovascular physical therapy for amputees. The effect of exercise on amputated leg blood flow (LBF) may potentially be altered due to voluntary muscle contractions after loss of the lower leg compared with the healthy leg. Case Presentation: A 57-year-old male patient with Burger disease attempted 3 min unilateral repeat/dynamic knee extensor exercise at a target muscle contraction frequency (1 s thigh muscle contraction and 1 s relaxation, 90 repetitions) with each leg <right transtibial amputated leg (AL) using a total surface-bearing prosthesis (TSB) and left non-AL> at six different contraction intensities (rubber resistance belt). Simultaneous measurement of blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, leg vascular conductance (LVC), and peak muscle strength (PMS) were performed during the 3 min exercise period. The maximum voluntary contraction by one-legged isometric knee muscle contraction was 14.7 kg in non-AL and 7.9 kg in the AL with prosthesis. The relative PMS was defined as “PMS/maximum voluntary contraction × 100 (%)”. Pre-exercise LBF was lower in the AL (200 ± 25 ml/min) than the non-AL (275 ± 74 ml/min). Both the non-AL and AL showed good positive linear relationships between absolute-/relative-PMS and LBF or LVC during 30 s at steady-state before the end of the exercise period. Furthermore, there was also similarity seen in the increase rate in LBF and/or LVC for the incremental relative PMS compared with the absolute PMS. Conclusion: In this case, the muscle strength depended on blood flow increase/vasodilation was seen in this “AL” using a TSB prosthesis for repeated dynamic knee extensor exercise. The present amputee’s limb muscle strengthening with the resection stump closely related to the degree of hyperemia in the amputated limb.
文摘In this study,Ulva prolifera protein was used for preparing angiotensin-I converting enzyme(ACE)-inhibitory peptide via virtual gastrointestinal digestion and in silico screening.Some parameters of the obtained peptide,such as inhibition kinetics,docking mechanism,stability,transport pathway,were explored by Lineweaver-Burk plots,molecular docking,in vitro stimulate gastrointestinal(GI)digestion and Caco-2 cells monolayer model,respectively.Then,a novel anti-ACE peptide LDF(IC_(50),(1.66±0.34)μmol/L)was screened and synthesized by chemical synthesis.It was a no-competitive inhibitor and its anti-ACE inhibitory effect mainly attributable to four Conventional Hydrogen Bonds and Zn701 interactions.It could keep activity during simulated GI digestion in vitro and was transported by peptide transporter PepT1 and passive-mediated mode.Besides,it could activate Endothelial nitric oxide synthase(eNOS)activity to promote the production of NO and reduce Endothelin-1(ET-1)secretion induced by AngiotensinⅡ(AngⅡ)in Human Umbilical Vein Endothelial Cells(HUVECs).Meanwhile,it could promote mice splenocytes proliferation in a concentration-dependent manner.Our study indicated that this peptide was a potential ingredient functioning on vasodilation and enhancing immunity.
文摘The binding of Fgn to GPIIb / IIIa has confirmed that there are two distinct amino acid sequences within the Fgn molecule that are responsible for mediating its attachment to GP IIb / IIIa receptor. In addition to monoclonal antibodies, the binding function of GP IIb / IIIa can be blocked by synthetic small peptides containing the RGD and APLRV sequence. In our preliminary study it was found that besides inhibition of platelet aggregation and thrombus formation RGDS showed vasodilation effects as well. In an attempt to confirm the vasodilation effect of RGDS related peptides, RGDF, APLRV, APLRVRGDS and APLRVRGDF were investigated. The effects of these synthetic peptides on rat aortic strips pretreated with NE in vitro were observed. The relaxing extents of contracted strips for the peptides at three doses (10 5 mol / L, 10 6 mol / L and 10 7 mol / L) were recorded.
文摘Background: The production of endothelial-derived factors induces either vasoconstriction or vasodilation;nitric oxide (NO) is the most distinguished relaxing factor. Endothelial dysfunction is associated with hypertension. The partial loss in the NO-promoted vasodilation is due to its decreased bioavailability and/or to an activity reduction of endothelium NO synthase (eNOS). Reactive oxygen species (ROS), present in oxidative stress, seize NO and diminish its bioavailability. Transresveratrol (RESV) has been proved to increase NO and eNOS levels. Thus, RESV could be capable of improving NO dependent vascular relaxation on aortic rings isolated from treated 2K-1C animals through ROS damage reduction. Aim: Evaluate the effects of RESV treatment on the relaxation of aortic rings isolated from treated 2K-1C rats while focusing on the effects of the treatment on systolic blood pressure. Methods: Male Wistar rats (180 g) were grouped: two 2K-1C and two Sham groups, one of each was treated with RESV (20 mg/kg, gavage) dissolved in Tween 80 and one of each was treated with water plus Tween 80 (control) for six weeks. The rats had their systolic blood pressure (SBP) measured before and after the treatments. Vascular reactivity studies were conducted in order to observe and compare acetylcholine (ACh)-induced relaxations in the presence and absence of the NOS inhibitor L-NAME (10-4 mol/L). Results: SBP for 2K-1C was significantly reduced in the treated group (179.13 ± 4.90 mmHg, n = 23) when compared to the untreated group (196.66 ± 6.06 mmHg, n = 15, p < 0.01). The maximum relaxation of aortic rings isolated from the 2K-1C treated group showed a higher efficacy (116.63% ± 1.72%, n = 12) than that from the untreated group (85.97% ± 0.69%, n = 6, p < 0.001);L-NAME exposure was responsible for a significant decrease in each group’s maximum relaxation efficacy. Conclusions: SBP reduction observed after RESV treatment in rat renal hypertension could be due to the reestablishment of vascular relaxation depend of NO.
基金Supported by the National Natural Science Foundation of China (No.81973589)。
文摘Objective:To develop an interference-free and rapid method to elucidate GuanxinⅡ(GXⅡ)'s representative vasodilator absorbed bioactive compounds(ABCs)among enormous phytochemicals.Methods:The contents of ferulic acid,tanshinol,and hydroxysafflor yellow A(FTA)in GXⅡ/rat serum after the oral administration of GXⅡ(30 g/kg)were detected using ultra-performance liquid chromatography-mass spectrometry.Totally 18 rats were randomly assigned to the control group(0.9%normal saline),GXⅡ(30 g/kg)and FTA(5,28 and 77 mg/kg)by random number table method.Diastolic coronary flow velocity-time integral(VTI),i.e.,coronary flow or coronary flow-mediated dilation(CFMD),and endothelium-intact vascular tension of isolated aortic rings were measured.After 12 h of exposure to blank medium or 0.5 mmol/L H_(2)O_(2),endothelial cells(ECs)were treated with post-dose GXⅡof supernatant from deproteinized serum(PGSDS,300μL PGSDS per 1 m L of culture medium)or FTA(237,1539,and 1510 mg/m L)for 10 min as control,H_(2)O_(2),PGSDS and FTA groups.Nitric oxide(NO),vascular endothelial growth factor(VEGF),endothelin-1(ET-1),superoxide dismutase(SOD),malondialdehyde(MDA)and phosphorylated phosphoinositide 3 kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),phosphorylated endothelial nitric oxide synthase(p-e NOS)were analyzed.PGSDS was developed as a GXⅡproxy of ex vivo herbal crude extracts.Results:PGSDS effectively eliminates false responses caused by crude GXⅡpreparations.When doses equaled the contents in GXⅡ/its post-dose serum,FTA accounted for 98.17%of GXⅡ-added CFMD and 92.99%of PGSDS-reduced vascular tension.In ECs,FTA/PGSDS was found to have significant antioxidant(lower MDA and higher SOD,P<0.01)and endothelial function-protective(lower VEGF,ET-1,P<0.01)effects.The increases in aortic relaxation,endothelial NO levels and phosphorylated PI3K/Akt/e NOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester(L-NA,e NOS inhibitor)and wortmannin(PI3K/AKT inhibitor),respectively,indicating an endothelium-dependent vasodilation via the PI3K/AKT-e NOS pathway(P<0.01).Conclusion:This study provides a strategy for rapidly and precisely elucidating GXⅡ's representative in/ex vivo cardioprotective absorbed bioactive compounds(ABCs)-FTA,suggesting its potential in advancing precision ethnomedicine.
基金Supported by Natural Science Foundation of Fujian Province(No.2018J01884)Science and Technology Major Project of Fujian Province(No.2019YZ014004)+1 种基金Fujian Provincial Health and Family Planning Commission(No.2018-CX-42)the National Natural Science Foundation of China(No.81774135)。
文摘Objective: To explore the effect of Kuanxiong Aerosol(KXA)on isoproterenol(ISO)-induced myocardial injury in rat models.Methods: Totally 24 rats were radomly divided into control,ISO,KXA low-dose and high-dose groups according to the randomized block design method,and were administered by intragastric administration for 10 consecutive days,and on the 9th and 10th days,rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA.In addition,the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test.The influence of KXA on the expression of calcium-CaM-dependent protein kinase Ⅱ(CaMK Ⅱ)/extracellular regulated protein kinases(ERK)signaling pathway has also been tested.Results: KXA significantly reduced the ISO-induced increase in ST-segment,interventricular septal thickness,cardiac mass index and cardiac tissue pathological changes in rats.Moreover,the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine(NE)or potassium chloride(KCl)was increased after KXA treatment in an endothelium-independent manner,and was attenuated by preincubation with verapamil,but not with tetraethylammonium chloride,4-aminopyridine,glibenclamide,or barium chloride.KXA pretreatment attenuated vasoconstriction induced by CaCl_(2)in Ca^(2+)-free solutions containing K^(+) or NE.In addition,KXA pretreatment inhibited accumulation of Ca^(2+)in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK Ⅱ and p-ERK levels.Conclusion: KXA may inhibit influx and release of calcium and activate the CaMK Ⅱ/ERK signaling pathway to produce vasodilatory effects,thereby improving myocardial injury.
基金supported in part by the National Institutes of Health(NIHgrant numbers:R01 ROl HL70562,HD 105699,and R21 HD097498 to Dong-bao Chen).
文摘Normal pregnancy is associated with dramatically increased estrogen biosynthesis whose role is believed to raise uterine blood flow to facilitate the bi-directional maternal-fetal exchanges of gases(O_(2) and CO_(2)),to deliver nutrients,and exhaust wastes to support fetal development and survival.Constrained uterine blood flow in pregnancy is a leading cause of preeclampsia with fetal growth restriction,rendering investigations of uterine hemodynamics to hold a high promise to inform pathways as targets for therapeutic interventions for preeclampsia.The mechanisms of estrogen-induced uterine vasodilation in pregnancy have long been attributed to enhanced endothelium production of nitric oxide,but clinical trials targeting this pathway that dominates uterine hemodynamics have achieved no to little success.Emerging evidence has recently shown a novel proangiogenic vasodilatory role of hydrogen sulfide in regulating uterine hemodynamics in pregnancy and preeclampsia,provoking a new field of perinatal research in searching for alternative pathways for pregnancy disorders especially preeclampsia and intrauterine growth restriction.This minireview is intended to summarize the nitric oxide pathway and to discuss the emerging hydrogen sulfide pathway in modulating estrogen-induced uterine vasodilation in pregnancy and preeclampsia.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81170725, 81070672, 81000316）, the Key Project of Science and Technology Department of Hunan Province of China （No. 2010SK2007）, Hunan Provincial Natural Science Foundation of China （No. 11JJ7005）, the National Department Public Benefit （Health） Research Foundation of China （No. 201002002）, the International Cooperation and Exchange of the National Natural Science Foundation of China （No. 30831160518）.
文摘Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study. Methods In the prospective study, we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years. Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia and obesity. We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay, endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound. At year 8, 102 patients were reexamined for endothelium-dependent and -independent vasodilation. Results Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline （r=0.150, P=0.043） and at year 8 （r=0.339, P=0.001）, whereas no association was found between adiponectin and endothelium-dependent vasodilation. In a stepwise multivariate linear regression model, adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 （P=0.001）. Conclusions Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention. These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.
文摘Objectives To investigate whether lovastatin improves endothelium dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals, as compared with L arginine. Methods Forty male rabbits, randomized into four groups with ten in each group, were fed with one of the following diets: ① normal rabbit chow; ② 1% cholesterol diet; ③ 1% cholesterol diet supplemented with 2.25 g/kg L arginine soluble in the physiological salt solution (PPS) by gavage; ④ 1% cholesterol diet supplemented with 10 mg/kg lovastatin soluble in the PSS by gavage. The rabbits were fed with these diets for 10 weeks, and blood samples were collected from animals for biochemical studies. Then aortic rings were obtained, and changes in isometric tension were recorded. Intimal atherosclerotic areas of the aortae were subsequently measured by planimetry. Results Serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL C) levels were lower￣ ed (30%±6%, 39%±4%, respectively) and high Department of Cardiovascular Internal Medicine, First Affiliated Hospital, Henan Medical University, Zhengzhou 450052, China (Zhang JY, Dong JZ, Li L, Zhao LS, Huang ZW, Wei JH and Liu RY) This work was supported by the Education Committee of Henan Province, China, and a grant from the Henan Science and Technology Committee. density lipoprotein cholesterol (HDL C) elevated (11%±3%) in the rabbits receiving 1% cholesterol diet supplemented with lovastatin, compared with those (including TC, LDL C, and HDL C) in the rabbits receiving 1% cholesterol diet and 1% cholesterol diet supplemented with L arginine, with alteration to the same degree. Endothelium dependent relaxations to acetylcholine were significantly impaired in aortae from the animals fed with a 1% cholesterol diet. By contrast, vessels from the hypercholesterolemic animals both receiving L arginine and lovastatin supplementation revealed significantly improved endothelium dependent relaxations. In addition, vessels from the hypercholesterolemic animals receiving L arginine were superior to those from those receiving lovastatin. Histomorphometric analysis showed a reduction in lesion surface area in aortae from the arginine and lovastatin supplemented animals compared to those from untreated hypercholesterolemic rabbits, moreover, lesion surface areas in aortae from both the arginine and lovastatin supplemented animals were similar (P>0.05). Conclusions This study demonstrates that lovastatin could improve endothelium dependent vasorelaxation. By contrast, L arginine is superior to lovastatin, but a reduced surface area in aortae is not different between the two drugs.
文摘Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to induce coronary vasospasm remains largely underreported.[1]Minoxidil is currently reserved for treating alopecia for various causes.
文摘BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral and non-viral etiologies are treated by traditional ARDS protocols that recommend 12-16 hours of prone position ventilation(PPV)with neuromuscular blocking agents(NMBA)and a trial of inhaled vasodilators(IVd)if oxygenation does not improve.However,debate on the efficacy of adjuncts to PPV and low tidal volume ventilation persists and evidence about the benefits of IVd/NMBA in COVID ARDS is sparse.In our multi-center retrospective review,we evaluated the impact of PPV,IVd,and NMBA on outcomes and lung mechanics in COVID ARDS patients with moderate to severe ARDS.AIM To evaluate the impact of PPV used alone or in combination with pulmonary IVd and/or NMBA in mechanically ventilated patients with moderate to severe ARDS during the COVID-19 pandemic.METHODS A retrospective study at two tertiary academic medical centers compared outcomes between COVID ARDS patients receiving PPV and patients in the supine position.PPV patients were divided based on concurrent use of ARDS adjunct therapies resulting in four subgroups:(1)PPV alone;(2)PPV and IVd;(3)PPV and NMBA;and(4)PPV,IVd,and NMBA.Primary outcomes were hospital and intensive care unit(ICU)length of stay(LOS),mortality,and venovenous extracorporeal membrane oxygenation(VV-ECMO)status.Secondary outcomes included changes in lung mechanics at 24-hour intervals for 7 days.RESULTS Total 114 patients were included in this study.Baseline respiratory parameters and Sequential Organ Failure Assessment scores were significantly worse in the PPV group.ICU LOS and LOS were significantly longer for patients who were proned,but no mortality benefit or difference in VV-ECMO status was found.Among the subgroups,no difference in primary outcomes were found.In the secondary analysis,PPV was associated with a significant improvement in arterial oxygen partial pressure(PaO_(2))/fractional inspired oxygen(FiO_(2))(P/F)ratio from day 1 to day 4(P<0.05)and higher driving pressures day 5 to day 7(P<0.05).The combination of PPV and IVd together resulted in improvements in P/F ratio from day 1 to day 7 and plateau pressure on day 4 and day 6(P<0.05).PPV with NMBA was not associated with improvements in any of the secondary outcomes.The use of all three rescue therapies together resulted in improvements in lung compliance on day 2(P<0.05)but no other improvements.CONCLUSION In mechanically ventilated patients diagnosed with moderate to severe COVID ARDS,PPV and PPV with the addition of IVd produced a significant and sustained increase in P/F ratio.The combination of PPV,IVd and NMBA improved compliance however this did not reach significance.Mortality and LOS did not improve with adjunct therapies.Further research is warranted to determine the efficacy of these therapies alone and in combination in the treatment of COVID ARDS.
基金supported by National Natural Science Foundation of China(No.81470050)Beijing Natural Science Foundation(No.7122097)
文摘Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s amelioration of ischaemic stroke and its effective constituents remain unclear. The present study aimed to identify the effective constituents of BYHWD and to further explore its action mechanisms in the amelioration of ischaemic stroke by testing the activities of 15 absorbable chemical constituents of BYHWD with the same methods under the same conditions. The following actions of these 15 compounds were revealed： 1） Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-β-D-glucoside, paeonol, calycosin-7-O-β-D-glucoside, astraisofla- van-7-O-β-D-glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin A （Con A）-induced T lymphocyte proliferation; 2） Propyl gallate, calycosin-7-O-β-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced apoptosis in RAW264.7 cells; 3） Propyl gallate and formononetin significantly inhibited LPS-induced NO release; 4） Hydroxysaffior yellow A and inosine protected PC12 cells against the injuries caused by glutamate; and 5） Formononetin, astragaloside IV, astraisofiavan-7-O-β-D- glucoside, inosine, paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid significantly suppressed the constriction of the thoracic aorta induced by KCI in rats. In conclusion, the results from the present study suggest that BYHWD exerts its ischaemic stroke ameliorating activities by modulating multiple targets with multiple components.
文摘Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.
基金supported by the National Natural Science Foundation of China(Nos.30960450,81173110)Yunnan Provincial Science and Technology Department(Nos.2011FA 022,2012BC012,2014FA010,2014FB037,2014BC012)
文摘Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction(ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate(c GMP) dependent protein kinase(PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and-independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU(10–1 000 μmol·L-1) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-c GMPS(PKGI-rp, 4 μmol·L-1), significantly blocked SCU(10–1 000 μmol·L-1)-induced relaxation. The NO synthase(NOS) inhibitor, NO-nitro-L-arginine methylester(L-NAME, 100 μmol·L-1), did not significantly change the effects of SCU(10–1 000 μmol·L-1). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU(500 μmol·L-1), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp(4 μmol·L-1) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein(p-VASP,phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.
文摘AIM:Adrenomedullin (ADM) is a potent vasodilator peptide. ADM and nitric oxide (NO) are produced in vascular endothelial cells.Increased ADM level has been linked to hyperdynamic circulation and arterial vasodilatation in cirrhotic portal hypertension (CPH).The role of ADM in non-cirrhotic portal hypertension (NCPH) is unknown,plasma ADM levels were studied in patients with NCPH,compensated and decompensated cirrhosis in order to determine its contribution to portal hypertension (PH) in these groups. METHODS:There were 4 groups of subjects.Group 1 consisted of 27 patients (F/M:12/15) with NCPH due to portal and/or splenic vein thrombosis (mean age:41±12 years),group 2 consisted of 14 patients (F/M:6/8) with compensated (Child-Pugh A) cirrhosis (mean age:46±4), group 3 consisted of 16 patients (F/M:6/10) with decompensated (Child-Pugh C) cirrhosis (mean age:47±12). Fourteen healthy subjects (F/M:6/8) (mean age:44±8) were used as controls in Group 4.ADM level was measured by ELISA.NO was determined as nitrite/nitrate level by chemoluminescence. RESULTS:ADM level in Group 1 (236±61.4 pg/mL) was significantly higher than that in group 2 (108.4±28.3 pg/mL) and group 4 (84.1±31.5 pg/mL) (both P<0.0001) but was lower than that in Group3 (324±93.7 pg/mL) (P=0.002).NO level in group 1 (27±1.4 μmol/L) was significantly higher than that in group 2 (19.8±2.8 μmol/L) and group 4 (16.9±1.6 μmol/L) but was lower than that in Group 3 (39±3.6 μmol/L) (for all three P<0.0001).A strong correlation was observed between ADM and NO levels (r=0.827,P<0.0001). CONCLUSION:Adrenomedullin and NO levels were high in both non-cirrhotic and cirrhotic portal hypertension and were closely correlated,Adrenomedullin and NO levels increased proportionally with the severity of cirrhosis,and were significantly higher than those in patients with NCPH. Portal hypertension plays an important role in the increase of ADM and NO.Parenchymal damage in cirrhosis may contribute to the increase in these parameters.
文摘Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.
