A series of novel pyrazolo [ 4,3-d ] pyrimidin-7-ones was designed and synthesized in order to find new potent phosphodiesterase 5 inhibitors（PDE5）. The structures of all the compounds were confirmed by IR, ^1H NMR ...A series of novel pyrazolo [ 4,3-d ] pyrimidin-7-ones was designed and synthesized in order to find new potent phosphodiesterase 5 inhibitors（PDE5）. The structures of all the compounds were confirmed by IR, ^1H NMR and MS; their in vitro vasodilatory activities were tested on isolated rabbit aortic spiral strips. Among them, compound X3 displays a significant vasodilatory activity, which is more potent than verapamil.展开更多
Objective:To investigate the vasodilatory effecl of Thymus serrulatus(T.serrulatus) aqueous leaf extract on KCl(high K^+.80 mmol/L) induced precontracted isolated thoracic aorta rings on guinea pigs and the role of ao...Objective:To investigate the vasodilatory effecl of Thymus serrulatus(T.serrulatus) aqueous leaf extract on KCl(high K^+.80 mmol/L) induced precontracted isolated thoracic aorta rings on guinea pigs and the role of aorta endothelium on this action.Methods:Guinea pig thoracic aorta was removed and placed in an organ bath containing Krebs-Henseleit solution and aorta contractions were recorded isometrically.Results:The results revealed that T.serrulalus aqueous leaf extract(0.5-5 mg/mL)significantly(P<0.001) reduced KCl-induced contractions of guinea pig thoracic aorta in both intact(n=5) and denuded(n=5) endothelium in a concentration dependent manner,and the vasodilatory effect of the extract on intact endothelium was significantly(P<0.05) higher than that on denuded endothelium.Glibenclamide(10 μmol/L) significantly(P<0.001) increased the vasodilatory effect of extract in intact endothelium as compared to methylene blue(10μmol/L).atropine(10 μmol/L) and indomethacin(10 μmol/L).The effecl was more obvious on intact than that on denuded endothelium.Conclusions:The present findings demonstrate that T.serrulalus aqueous leaf extract has vasodilator)' activity which might result in antihypertensive effect and its vasodilatory effect is endothelium-dependent.This might support the traditional claim of the plant in hypertensive.展开更多
Objective Vasopressin has showed a beneficial use in pediatric patients with vasodilatory shock after cardiac surgery. However, the optimal timing of vasopressin initiation has not been investigated.Our aim was to eva...Objective Vasopressin has showed a beneficial use in pediatric patients with vasodilatory shock after cardiac surgery. However, the optimal timing of vasopressin initiation has not been investigated.Our aim was to evaluate the effect of early vasopressin initiation for these patients.展开更多
A series of pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and tested for vasodilatory activities. All of them were new compounds and their structures were confirmed by IR, 1H NMR, MS and elemental analy...A series of pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and tested for vasodilatory activities. All of them were new compounds and their structures were confirmed by IR, 1H NMR, MS and elemental analysis.展开更多
Objective:To investigate the possible regulatory mechanism of corticotropin-releasing hormone(CRH),urocortin(UCN),and Wolfram syndrome 1(WFS1)in 17α-ethynylestradiol(EE)-induced intrahepatic cholestasis pregnant rats...Objective:To investigate the possible regulatory mechanism of corticotropin-releasing hormone(CRH),urocortin(UCN),and Wolfram syndrome 1(WFS1)in 17α-ethynylestradiol(EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion(IR)model.Methods:Pregnant rats(n=60)were randomly divided into four experimental groups by random number table(Control,EE,IR,and EE-IR groups),and were studied on the 17^(th),19th,and 21st gestational days(GD)(n=5 in each group at the indicated time).Growth and development indicators of fetal rats among these four groups were recorded.Enzyme-linked immunosorbent assay was employed to detect CRH,UCN,and WFS1 levels in maternal sera.Western blotting and real-time polymerase chain reaction were used to quantify placental protein and placental mRNA levels of CRH,UCN,and WFS1.Multivariate analysis of variance and least significant difference test were used to establish the group and individual comparisons.Results:A significant difference was found in placenta weight(F=8.10,P<0.05),fetal rat weight(F=40.86,P<0.05),fetal rat length(F=61.61,P<0.05),and fetal rat tail length(F=55.63,P<0.05)among four groups on the 17^(th),19th,and 21st GD.What’s more,the overall differences of maternal serum UCN levels among Control,EE,IR,and EE-IR groups were significant(F=2.48,P<0.05).Expression of WFS1 mRNA in the EE-IR group was significantly increased and higher than Control(0.46±0.15vs.0.24±0.09,P<0.05),EE(0.46±0.15vs.0.17±0.04,P>0.05),and IR(0.46±0.15vs.0.22±0.15,P>0.05)groups at 19th GD,indicating that endoplasmic reticulum stress may be activated.However,the expression of CRH(0.42±0.05vs.0.58±0.12,P<0.05),UCN(0.43±0.01vs.0.47±0.16,P>0.05),and WFS1(0.57±0.07vs.0.74±0.12,P>0.05)protein in the EE-IR group was subsided compared to the IR group at 17^(th) GD.Conclusion:Fetal rat growth restriction was found in the EE-induced intrahepatic cholestasis model.This study revealed that significant changes in the maternal sera level of UCN,placental level of WFS1 mRNA and placental levels of CRH,UCN,and WFS1 protein in chronic versus acute stress in a rat model of pregnancy.This suggests an impaired compensatory vasodilatory effect mediated by these factors at gene transcription and protein translation levels,following acute hypoxia stress in EE-induced intrahepatic cholestasis in pregnant rats.展开更多
Honokiol is a protective agent for cerebral ischemia injury when administered intravenously. In the present study, we aimed to investigate the oral effect of honokiol microemulsion on cerebral isehemia-reperfusion （...Honokiol is a protective agent for cerebral ischemia injury when administered intravenously. In the present study, we aimed to investigate the oral effect of honokiol microemulsion on cerebral isehemia-reperfusion （I-R） injury in rats and stroke in SHRsp. Both tMCAO and SHRsp models in rats were used to evaluate the efficacy of the microemulsion. Rat aortic segment contraction test, primary rat aortic endothelial cells and primary brain microvascular endothelial cells （BMECs） injured by OGD-R were used to explore its potential action mechanism. Oral honokiol microemulsion significantly reduced infarct volume, neurological score and brain water content in tMCAO model, and it evidently reduced neurological score and increased the survival rate of SHRsp. Moreover, honokiol significantly inhibited aortic contraction induced by KC1 and phenylephrine, and L-NAME suppressed these inhibitory effects. On the other side, honokiol increased NO and p-eNOS levels in rat endothelial cells. In addition, it also protects BMECs against OGD-R injury and increased eNOS expression in BMECs. In conclusion, oral honokiol administration has protective effects in tMCAO and in SHRsp rats, and its action mechanism is likely to be associated with its vasodilative effect produced by eNOS activation and with its protective effect on BMECs.展开更多
BACKGROUND The initial trials on angiotensin Ⅱ(AT Ⅱ)administration indicated a high incidence of thrombocytopenia and thrombosis,as well as a positive correlation between hyperreninemia and response to the medicatio...BACKGROUND The initial trials on angiotensin Ⅱ(AT Ⅱ)administration indicated a high incidence of thrombocytopenia and thrombosis,as well as a positive correlation between hyperreninemia and response to the medication.CASE SUMMARY We describe a case of a patient presenting with catecholamine resistant septic shock,thrombocytopenia,deep vein thrombosis,and normal renin concentration who responded immediately to AT Ⅱ treatment.We observed no worsening of thrombocytopenia and no progression of thrombosis or additional thromboses during treatment.CONCLUSION Our case underscores the need for individualized assessment of patients for potential therapy with AT Ⅱ.展开更多
基金Supported by the Natural Science Foundation of Liaoning Province(No. 20032043)
文摘A series of novel pyrazolo [ 4,3-d ] pyrimidin-7-ones was designed and synthesized in order to find new potent phosphodiesterase 5 inhibitors（PDE5）. The structures of all the compounds were confirmed by IR, ^1H NMR and MS; their in vitro vasodilatory activities were tested on isolated rabbit aortic spiral strips. Among them, compound X3 displays a significant vasodilatory activity, which is more potent than verapamil.
基金Supported by Ministry of Finance and Econonmic Development(Project No.342/02/04/01/013)
文摘Objective:To investigate the vasodilatory effecl of Thymus serrulatus(T.serrulatus) aqueous leaf extract on KCl(high K^+.80 mmol/L) induced precontracted isolated thoracic aorta rings on guinea pigs and the role of aorta endothelium on this action.Methods:Guinea pig thoracic aorta was removed and placed in an organ bath containing Krebs-Henseleit solution and aorta contractions were recorded isometrically.Results:The results revealed that T.serrulalus aqueous leaf extract(0.5-5 mg/mL)significantly(P<0.001) reduced KCl-induced contractions of guinea pig thoracic aorta in both intact(n=5) and denuded(n=5) endothelium in a concentration dependent manner,and the vasodilatory effect of the extract on intact endothelium was significantly(P<0.05) higher than that on denuded endothelium.Glibenclamide(10 μmol/L) significantly(P<0.001) increased the vasodilatory effect of extract in intact endothelium as compared to methylene blue(10μmol/L).atropine(10 μmol/L) and indomethacin(10 μmol/L).The effecl was more obvious on intact than that on denuded endothelium.Conclusions:The present findings demonstrate that T.serrulalus aqueous leaf extract has vasodilator)' activity which might result in antihypertensive effect and its vasodilatory effect is endothelium-dependent.This might support the traditional claim of the plant in hypertensive.
文摘Objective Vasopressin has showed a beneficial use in pediatric patients with vasodilatory shock after cardiac surgery. However, the optimal timing of vasopressin initiation has not been investigated.Our aim was to evaluate the effect of early vasopressin initiation for these patients.
文摘A series of pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and tested for vasodilatory activities. All of them were new compounds and their structures were confirmed by IR, 1H NMR, MS and elemental analysis.
基金supported by the National Natural Science Foundation of China(Grant No.81571446)the National Natural Science Foundation for Young Scientists of China(Grant No.82001560).
文摘Objective:To investigate the possible regulatory mechanism of corticotropin-releasing hormone(CRH),urocortin(UCN),and Wolfram syndrome 1(WFS1)in 17α-ethynylestradiol(EE)-induced intrahepatic cholestasis pregnant rats and its ischemia reperfusion(IR)model.Methods:Pregnant rats(n=60)were randomly divided into four experimental groups by random number table(Control,EE,IR,and EE-IR groups),and were studied on the 17^(th),19th,and 21st gestational days(GD)(n=5 in each group at the indicated time).Growth and development indicators of fetal rats among these four groups were recorded.Enzyme-linked immunosorbent assay was employed to detect CRH,UCN,and WFS1 levels in maternal sera.Western blotting and real-time polymerase chain reaction were used to quantify placental protein and placental mRNA levels of CRH,UCN,and WFS1.Multivariate analysis of variance and least significant difference test were used to establish the group and individual comparisons.Results:A significant difference was found in placenta weight(F=8.10,P<0.05),fetal rat weight(F=40.86,P<0.05),fetal rat length(F=61.61,P<0.05),and fetal rat tail length(F=55.63,P<0.05)among four groups on the 17^(th),19th,and 21st GD.What’s more,the overall differences of maternal serum UCN levels among Control,EE,IR,and EE-IR groups were significant(F=2.48,P<0.05).Expression of WFS1 mRNA in the EE-IR group was significantly increased and higher than Control(0.46±0.15vs.0.24±0.09,P<0.05),EE(0.46±0.15vs.0.17±0.04,P>0.05),and IR(0.46±0.15vs.0.22±0.15,P>0.05)groups at 19th GD,indicating that endoplasmic reticulum stress may be activated.However,the expression of CRH(0.42±0.05vs.0.58±0.12,P<0.05),UCN(0.43±0.01vs.0.47±0.16,P>0.05),and WFS1(0.57±0.07vs.0.74±0.12,P>0.05)protein in the EE-IR group was subsided compared to the IR group at 17^(th) GD.Conclusion:Fetal rat growth restriction was found in the EE-induced intrahepatic cholestasis model.This study revealed that significant changes in the maternal sera level of UCN,placental level of WFS1 mRNA and placental levels of CRH,UCN,and WFS1 protein in chronic versus acute stress in a rat model of pregnancy.This suggests an impaired compensatory vasodilatory effect mediated by these factors at gene transcription and protein translation levels,following acute hypoxia stress in EE-induced intrahepatic cholestasis in pregnant rats.
基金National Natural Science Foundation of China(Grant No.81503060)
文摘Honokiol is a protective agent for cerebral ischemia injury when administered intravenously. In the present study, we aimed to investigate the oral effect of honokiol microemulsion on cerebral isehemia-reperfusion （I-R） injury in rats and stroke in SHRsp. Both tMCAO and SHRsp models in rats were used to evaluate the efficacy of the microemulsion. Rat aortic segment contraction test, primary rat aortic endothelial cells and primary brain microvascular endothelial cells （BMECs） injured by OGD-R were used to explore its potential action mechanism. Oral honokiol microemulsion significantly reduced infarct volume, neurological score and brain water content in tMCAO model, and it evidently reduced neurological score and increased the survival rate of SHRsp. Moreover, honokiol significantly inhibited aortic contraction induced by KC1 and phenylephrine, and L-NAME suppressed these inhibitory effects. On the other side, honokiol increased NO and p-eNOS levels in rat endothelial cells. In addition, it also protects BMECs against OGD-R injury and increased eNOS expression in BMECs. In conclusion, oral honokiol administration has protective effects in tMCAO and in SHRsp rats, and its action mechanism is likely to be associated with its vasodilative effect produced by eNOS activation and with its protective effect on BMECs.
文摘BACKGROUND The initial trials on angiotensin Ⅱ(AT Ⅱ)administration indicated a high incidence of thrombocytopenia and thrombosis,as well as a positive correlation between hyperreninemia and response to the medication.CASE SUMMARY We describe a case of a patient presenting with catecholamine resistant septic shock,thrombocytopenia,deep vein thrombosis,and normal renin concentration who responded immediately to AT Ⅱ treatment.We observed no worsening of thrombocytopenia and no progression of thrombosis or additional thromboses during treatment.CONCLUSION Our case underscores the need for individualized assessment of patients for potential therapy with AT Ⅱ.
