Renin is the rate-limiting enzyme of the reninangiotensin system (RAS). In addition to its enzymatic activity to generate angiotensin I, renin also signals through the (pro)renin receptor to exert angiotensin II-indep...Renin is the rate-limiting enzyme of the reninangiotensin system (RAS). In addition to its enzymatic activity to generate angiotensin I, renin also signals through the (pro)renin receptor to exert angiotensin II-independent effects. In this study we examined the effect of renin inhibition on the development of diabetic nephropathy. Male DBA/2J mice were induced to diabetes with streptozotocin, and the diabetic mice were treated for 16 weeks with saline or aliskiren, a renin enzymatic inhibitor. Aliskiren treatment had little effects on blood glucose and blood pressure in diabetic mice. Saline-treated mice developed progressive albuminuria and glome-rulosclerosis, and aliskiren treatment effectively alleviated albumiuria and glomerulosclerosis. Morphologically aliskiren treatment prevented the thickening of the glomerular basement membrane and reduced podocyte loss. At the molecular levels, aliskiren prevented the decline of slit diaphragm proteins and blocked the synthesis of extracellular matrix and pro-fibrotic factors in the diabetic kidney. Aliskiren treatment results in compensatory renin increase in the glomeruli due to blockade of the negative feedback loop, and also partially suppressed the intracellular signaling mediated by the (pro)renin receptor activated in hyperglycemia. These observations suggest that the therapeutic activity of aliskiren to prevent diabetic renal injury is contributed by inhibition of both the angiotensin II-dependent and -independent pathways. Taken together, it is concluded that inhibition of renin enzymatic activity ameliorates diabetic renal injury in type 1 diabetes, and support the use of aliskiren in diabetes kidney disease.展开更多
ABSTRACT Importance Hospitalizations for heart failure （HHF） represent a major health burden, with high rates of early postdischarge rehospitalization and mortality. Objective To investigate whether aliskiren, a d...ABSTRACT Importance Hospitalizations for heart failure （HHF） represent a major health burden, with high rates of early postdischarge rehospitalization and mortality. Objective To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular （CV） death or HF rehospitalization among HHF patients. Design, Setting, and Participants International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction （LVEF） 40% or less,展开更多
AIM： To assess the effcacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease （CKD）.METHODS： This is a retrospective study of 143 pa-tients with non-diabetic CK...AIM： To assess the effcacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease （CKD）.METHODS： This is a retrospective study of 143 pa-tients with non-diabetic CKD comparing combined Aliskiren （150 mg/d） with Losartan （100 mg/d） therapy vs High dose Angiotensin receptor blockers （ARB） （Losartan 200 mg/d） and the third group Aliskiren （150 mg/d） alone. This study involved only patient medi-cal records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate （eGFR） 〈 15 mL/min or end stage renal failure. RESULTS： Patients treated with high dose ARB com-pared to the other two treatment groups had signifcantly less proteinuria at the end of 36 mo （ P 〈 0.007）. All 3 groups had signifcant reduction of proteinuria （ P 〈 0.043, P 〈 0.001）. Total urinary protein was signifcantly differ-ent between the 3 groups over the 3-year study period （ P = 0.008）, but not eGFR. The changes in eGFR from baseline to each year were not signifcantly different be-tween the 3 therapeutic groups （ P 〈 0.119）. There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia （〉 5.5 mmol/L） was 14.2% （7/49） in the Combined Aliskiren and ARB group, 8.7% （4/46） in the Aliskiren alone group and 6.3% （3/48） in the High dose ARB group （ P 〈 0.001）.CONCLUSION： This study in non-diabetic CKD pa-tients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was asso-ciated with a high prevalence of hyperkalaemia.展开更多
Hypertension is a serious problem that is recently thought to be associated with damaging effects on target organs partially via oxidative stress. On the other hand, there is accumulating literature describing some so...Hypertension is a serious problem that is recently thought to be associated with damaging effects on target organs partially via oxidative stress. On the other hand, there is accumulating literature describing some sort of therapeutic interaction between antioxidant enzymes in vital organs and hypertension. Therefore, the aim of this study is to investigate the possible effect of a direct renin inhibitor, aliskiren, used in treatment of hypertension via renin-angiotensin-aldosterone system (RAAS), on selected anti-oxidant enzymes in hepatic homogenates in DOCA salt-induced hypertesnive albino rats. Thirty male wister albino rats were assigned randomly into 3 groups (n = 10/ group). Group 1 received no treatement and serves as control. Group 2 received 0.5% carboxymethylcellulose sodium ip as a solvent of aliskiren, as a direct renin inhibitor (DRI). Group 3 received aliskiren 100 mg/kg/day ip for 4 weeks through gastric tube. Systolic blood pressure (SBP) was measured every week and its mean was recorded at the end of the study. Superoxide dismutase (SOD) enzyme in RBCs lysates, activities of catalase (CAT) and glutathione peroxidase enzymes and thiobarbituric acid reactive substance (TBARS), as a marker of lipid peroxidation, in hepatic homogenates were measured at the end of the study. DRI produced a marked reduction in mean SBP of hypertensive rats. It also significantly (p < 0.05) increased the activities of measured anti-oxidant enzymes while it significantly (p < 0.05) reduced TBARS in liver homogenates. These results indicated that renin possesses an oxidative effect in the liver in hypertensive rats. Aliskiren, in addition to its powerful anti-hypertensive effect, it could induce a great anti-oxidant effect in liver homogenates of DOCA salt-hypertensive rats.展开更多
Introduction: Treatment with renin-angiotensin-aldosterone-system (RAAS) blockers plays a major role in halting chonic kidney disease (CKD) progression. Aliskiren is the first orally available direct renin inhibitor (...Introduction: Treatment with renin-angiotensin-aldosterone-system (RAAS) blockers plays a major role in halting chonic kidney disease (CKD) progression. Aliskiren is the first orally available direct renin inhibitor (DRI). Objective: We studied the efficacy of aliskiren compared to losartan in patients with primary GN. Design and Method: This was a prospective open-label randomized control trial in patients with primary GN. Patients were randomized to receive either aliskiren or losartan to maximum tolerated doses for 24 weeks. Blood and urine investigations were measured at baseline and at 4-weekly intervals. Adverse effects were recorded. Results: 22 patients were recruited (aliskiren-11 and losartan-11). Their baseline characteristics were comparable with the exception of a higher proteinuria (uPCI) in the aliskiren arm. There were no significant differences in proteinuria, blood pressure and other renal parameters between both groups. At end-study, only patients in the aliskiren arm showed significant reductions in both the systolic blood pressure and in proteinuria. There were no changes in the other parameters of renal function over time and no adverse events occurred. Conclusion: Aliskiren appears to be as efficacious and tolerable as losartan both as an antihypertensive and antiproteinuric agent in this study.展开更多
We present a case of significant, persistent, and relatively refractory hypotension during general anesthesia in a reasonably healthy 50-year-old man thought to be caused by a direct rennin inhibitor. This case is of ...We present a case of significant, persistent, and relatively refractory hypotension during general anesthesia in a reasonably healthy 50-year-old man thought to be caused by a direct rennin inhibitor. This case is of particular significance because the medication thought responsible for the hemodynamic abnormalities is a relatively novel antihypertensive agent and remains largely unknown to clinical anesthesia providers.展开更多
Background Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. The aim of this study was to assess the effect of aliskiren on arterial stiffness, compared with that of ramipril...Background Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. The aim of this study was to assess the effect of aliskiren on arterial stiffness, compared with that of ramipril in mild to moderate essential hypertensive patients. Methods Following a two week placebo run-in period, patients with a mean sitting diastolic blood pressure （ms-DBP） 〉95 and 〈110 mmHg （1 mmHg=0.133 kPa）, and a mean sitting systolic blood pressure （ms-SBP） 〈180 mmHg were randomly allocated to treatment with aliskiren （150 mg/d, n=20） or ramipril （5 mg/d, n=20） for eight weeks. Blood pressure, plasma renin activity, and the brachial-ankle pulse wave velocity （ba-PWV） were measured before and after eight weeks of treatment. Results Eight weeks of treatment significantly decreased systolic blood pressure and diastolic blood pressure in both the aliskiren group and ramipril group. The hypotensJve effect did not differ between the two groups. Plasma renin activity decreased after aliskiren treatment and increased after ramipril treatment. There was no significant difference in baseline ba-PWV between the aliskiren and ramipril groups （P=-0.892）. The ba-PWV was significantly reduced in both the aliskiren group （1535 （1405-1666） vs. 1464 （1360-1506） cm/s） （P 〈0.01） and the ramipril group （1544 （1433-1673） vs. 1447 （1327-1549） cm/s） （P 〈0.01）. No statistically significant difference was found in the decline of ba-PWV between the two groups （P=0.766）. Conclusions The current study revealed that aliskiren （150 mg/d） could ameliorate arterial stiffness and its effect was similar to ramipril （5 mg/d） in mild to moderate hypertensive patients, indicating that in addition to lowering blood pressure, aliskiren had beneficial effect on vascular protection.展开更多
Background Aliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular ...Background Aliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated. Methods Male Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups： angiotensin converting enzyme inhibitor enalapril, angiotensin receptor blocker valsartan, 13 adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks. Electrophysiological study, histological examination and Western blotting were performed. Results The plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats. Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction. There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril, valsartan, carvediloand or aliskiren treated groups. Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced, ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats. Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats. Conclusions Aliskiren ameliorated cardiomyocytic apoptosis, attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction. Enalapril, valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis, sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.展开更多
文摘Renin is the rate-limiting enzyme of the reninangiotensin system (RAS). In addition to its enzymatic activity to generate angiotensin I, renin also signals through the (pro)renin receptor to exert angiotensin II-independent effects. In this study we examined the effect of renin inhibition on the development of diabetic nephropathy. Male DBA/2J mice were induced to diabetes with streptozotocin, and the diabetic mice were treated for 16 weeks with saline or aliskiren, a renin enzymatic inhibitor. Aliskiren treatment had little effects on blood glucose and blood pressure in diabetic mice. Saline-treated mice developed progressive albuminuria and glome-rulosclerosis, and aliskiren treatment effectively alleviated albumiuria and glomerulosclerosis. Morphologically aliskiren treatment prevented the thickening of the glomerular basement membrane and reduced podocyte loss. At the molecular levels, aliskiren prevented the decline of slit diaphragm proteins and blocked the synthesis of extracellular matrix and pro-fibrotic factors in the diabetic kidney. Aliskiren treatment results in compensatory renin increase in the glomeruli due to blockade of the negative feedback loop, and also partially suppressed the intracellular signaling mediated by the (pro)renin receptor activated in hyperglycemia. These observations suggest that the therapeutic activity of aliskiren to prevent diabetic renal injury is contributed by inhibition of both the angiotensin II-dependent and -independent pathways. Taken together, it is concluded that inhibition of renin enzymatic activity ameliorates diabetic renal injury in type 1 diabetes, and support the use of aliskiren in diabetes kidney disease.
文摘ABSTRACT Importance Hospitalizations for heart failure （HHF） represent a major health burden, with high rates of early postdischarge rehospitalization and mortality. Objective To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular （CV） death or HF rehospitalization among HHF patients. Design, Setting, and Participants International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction （LVEF） 40% or less,
基金Supported by Singhealth Cluster with IRB approval,CIRB Ref:569E
文摘AIM： To assess the effcacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease （CKD）.METHODS： This is a retrospective study of 143 pa-tients with non-diabetic CKD comparing combined Aliskiren （150 mg/d） with Losartan （100 mg/d） therapy vs High dose Angiotensin receptor blockers （ARB） （Losartan 200 mg/d） and the third group Aliskiren （150 mg/d） alone. This study involved only patient medi-cal records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate （eGFR） 〈 15 mL/min or end stage renal failure. RESULTS： Patients treated with high dose ARB com-pared to the other two treatment groups had signifcantly less proteinuria at the end of 36 mo （ P 〈 0.007）. All 3 groups had signifcant reduction of proteinuria （ P 〈 0.043, P 〈 0.001）. Total urinary protein was signifcantly differ-ent between the 3 groups over the 3-year study period （ P = 0.008）, but not eGFR. The changes in eGFR from baseline to each year were not signifcantly different be-tween the 3 therapeutic groups （ P 〈 0.119）. There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia （〉 5.5 mmol/L） was 14.2% （7/49） in the Combined Aliskiren and ARB group, 8.7% （4/46） in the Aliskiren alone group and 6.3% （3/48） in the High dose ARB group （ P 〈 0.001）.CONCLUSION： This study in non-diabetic CKD pa-tients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was asso-ciated with a high prevalence of hyperkalaemia.
文摘Hypertension is a serious problem that is recently thought to be associated with damaging effects on target organs partially via oxidative stress. On the other hand, there is accumulating literature describing some sort of therapeutic interaction between antioxidant enzymes in vital organs and hypertension. Therefore, the aim of this study is to investigate the possible effect of a direct renin inhibitor, aliskiren, used in treatment of hypertension via renin-angiotensin-aldosterone system (RAAS), on selected anti-oxidant enzymes in hepatic homogenates in DOCA salt-induced hypertesnive albino rats. Thirty male wister albino rats were assigned randomly into 3 groups (n = 10/ group). Group 1 received no treatement and serves as control. Group 2 received 0.5% carboxymethylcellulose sodium ip as a solvent of aliskiren, as a direct renin inhibitor (DRI). Group 3 received aliskiren 100 mg/kg/day ip for 4 weeks through gastric tube. Systolic blood pressure (SBP) was measured every week and its mean was recorded at the end of the study. Superoxide dismutase (SOD) enzyme in RBCs lysates, activities of catalase (CAT) and glutathione peroxidase enzymes and thiobarbituric acid reactive substance (TBARS), as a marker of lipid peroxidation, in hepatic homogenates were measured at the end of the study. DRI produced a marked reduction in mean SBP of hypertensive rats. It also significantly (p < 0.05) increased the activities of measured anti-oxidant enzymes while it significantly (p < 0.05) reduced TBARS in liver homogenates. These results indicated that renin possesses an oxidative effect in the liver in hypertensive rats. Aliskiren, in addition to its powerful anti-hypertensive effect, it could induce a great anti-oxidant effect in liver homogenates of DOCA salt-hypertensive rats.
文摘Introduction: Treatment with renin-angiotensin-aldosterone-system (RAAS) blockers plays a major role in halting chonic kidney disease (CKD) progression. Aliskiren is the first orally available direct renin inhibitor (DRI). Objective: We studied the efficacy of aliskiren compared to losartan in patients with primary GN. Design and Method: This was a prospective open-label randomized control trial in patients with primary GN. Patients were randomized to receive either aliskiren or losartan to maximum tolerated doses for 24 weeks. Blood and urine investigations were measured at baseline and at 4-weekly intervals. Adverse effects were recorded. Results: 22 patients were recruited (aliskiren-11 and losartan-11). Their baseline characteristics were comparable with the exception of a higher proteinuria (uPCI) in the aliskiren arm. There were no significant differences in proteinuria, blood pressure and other renal parameters between both groups. At end-study, only patients in the aliskiren arm showed significant reductions in both the systolic blood pressure and in proteinuria. There were no changes in the other parameters of renal function over time and no adverse events occurred. Conclusion: Aliskiren appears to be as efficacious and tolerable as losartan both as an antihypertensive and antiproteinuric agent in this study.
文摘We present a case of significant, persistent, and relatively refractory hypotension during general anesthesia in a reasonably healthy 50-year-old man thought to be caused by a direct rennin inhibitor. This case is of particular significance because the medication thought responsible for the hemodynamic abnormalities is a relatively novel antihypertensive agent and remains largely unknown to clinical anesthesia providers.
文摘Background Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. The aim of this study was to assess the effect of aliskiren on arterial stiffness, compared with that of ramipril in mild to moderate essential hypertensive patients. Methods Following a two week placebo run-in period, patients with a mean sitting diastolic blood pressure （ms-DBP） 〉95 and 〈110 mmHg （1 mmHg=0.133 kPa）, and a mean sitting systolic blood pressure （ms-SBP） 〈180 mmHg were randomly allocated to treatment with aliskiren （150 mg/d, n=20） or ramipril （5 mg/d, n=20） for eight weeks. Blood pressure, plasma renin activity, and the brachial-ankle pulse wave velocity （ba-PWV） were measured before and after eight weeks of treatment. Results Eight weeks of treatment significantly decreased systolic blood pressure and diastolic blood pressure in both the aliskiren group and ramipril group. The hypotensJve effect did not differ between the two groups. Plasma renin activity decreased after aliskiren treatment and increased after ramipril treatment. There was no significant difference in baseline ba-PWV between the aliskiren and ramipril groups （P=-0.892）. The ba-PWV was significantly reduced in both the aliskiren group （1535 （1405-1666） vs. 1464 （1360-1506） cm/s） （P 〈0.01） and the ramipril group （1544 （1433-1673） vs. 1447 （1327-1549） cm/s） （P 〈0.01）. No statistically significant difference was found in the decline of ba-PWV between the two groups （P=0.766）. Conclusions The current study revealed that aliskiren （150 mg/d） could ameliorate arterial stiffness and its effect was similar to ramipril （5 mg/d） in mild to moderate hypertensive patients, indicating that in addition to lowering blood pressure, aliskiren had beneficial effect on vascular protection.
基金This study was supported by grants trom Natural Science Foundation of China （No. 30971223） and Nantong Society Development Project （No. 2010008）.
文摘Background Aliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated. Methods Male Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups： angiotensin converting enzyme inhibitor enalapril, angiotensin receptor blocker valsartan, 13 adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks. Electrophysiological study, histological examination and Western blotting were performed. Results The plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats. Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction. There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril, valsartan, carvediloand or aliskiren treated groups. Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced, ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats. Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats. Conclusions Aliskiren ameliorated cardiomyocytic apoptosis, attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction. Enalapril, valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis, sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.
