Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways

Aliskiren (ALS) is well known for its antihypertensive properties. However, the potential underlying the molecular mechanism and the anti-hypertrophic effect of ALS have not yet been fully elucidated. The aim of the present study was to investigate the role of ALS in mammalian target of rapamycin (mTOR) and apoptosis signaling using in vivo and in vitro models of cardiac hypertrophy. A rat model of cardiac hypertrophy was induced by isoproterenol treatment (5 mg·kg-1·day-1) for 4 weeks, with or without ALS treatment at 20 mg·kg-1·day-1. The expression of hypertrophic, fibrotic, and apoptotic markers was determined by RT-qPCR. The protein expression of apoptotic markers mTOR and p-mTOR was assessed by western blot analysis. The proliferation of H9C2 cells was monitored using the MTS assay. Cell apoptosis was analyzed using flow cytometry. In vivo, isoproterenol-treated rats exhibited worse cardiac function, whereas ALS treatment reversed these dysfunctions, which were associated with changes in p-mTOR, Bcl-2, Bax, and cleaved caspase-3 expression, as well as the number of apoptotic cells. In vitro, H9C2 cardiomyocyte viability was significantly inhibited and cardiac hypertrophy was induced by Ang II administration, but ALS reversed Ang II-induced H9C2 cardiomyocyte hypertrophy and death. Furthermore, Ang II triggered the activation of the mTOR and apoptosis pathways in hypertrophic cardiomyocytes that were inhibited by ALS treatment. These results indicated that ALS alleviated cardiac hypertrophy through inhibition of the mTOR and apoptosis pathways in cardiomyocytes.

Aliskiren and losartan study in non-diabetic CKD: a comparison of patients in the clinical trial versus the usual care group

Background: This is a comparative study of a 6 year retrospective analysis of the therapeutic efficacy and safety of Combined Aliskiren (150 mg a day) and Losartan (100 mg a day) in a Clinical Trial setting versus a Usual Care group of patients on Losartan (100 mg a day), Telmisartan (80 mg a day) and Combined Enalapril (10 mg a day) plus Losartan (100mg a day) in non-Diabetic Chronic Kidney Disease (CKD) patients. The objective of this study was to ascertain if there were any differences in the renal outcome of patients treated within a Clinical Trial setting versus a Usual Care setting. The study seeks to establish the relevance of having a Usual Care group as a comparator and whether its inclusion in the study would help to validate the findings in the Clinical Trial group Methods: This is a 2nd Phase follow up study three years after the initial 1st Phase study in the Clinical Trial Group. Patients in the 2nd Phase study were those who continued to have proteinuria and were treated with Losartan 100mg a day. The 2nd Phase study seeks to document the incidence of remission of proteinuria following their initial 1st Phase therapy for proteinuria compared to those in the Usual Care group where treatment remained unchanged from year 1 to end of year 6. The rates of remission of proteinuria and improvement of renal function as well as associated comorbidities between the 2 groups are compared. Results: Among the 154 patients in the Clinical Trial Group, 70/154 (45%) continued to have proteinuria, while 84/154 (55%) had no proteinuria (remission) compared to 41 (28%) in remission and 104 (72%) with continued proteinuria in the Usual Care group (p<0.001). There were more patients with hypertension and yperkalaemia in the Clinical Trial group compared to the Usual Care group. Seven patients were in ESRF in the Usual Care group compared to only 3 in the Clinical Trial group but this difference was not significant. More patients in the Clinical Trial group compared to the Usual Care group had improvement in eGFR at the end of the 6 years (p<0.001). Conclusions: This study shows that patients in a Clinical Trial setting do better than those in the Usual Care setting as they are more likely to have improvement in renal function with remission of proteinuria.

Efecto del aliskireno sobre la angiogénesis en modelo de membrana alantocoriónica (MAC) de pollo / Effect of aliskiren on angiogenesis in chick embryo chorioallantoic membrane (CAM) assay

La acción antiangiogénica de los inhibidores del receptor de angiotensina II (ARA II), ha sido documentada previamente, sin embargo, no ha sido descrita la relación entre angiogénesis e inhibidores directos de la renina (DRIs), los cuales participan regulando el sistema renina-angiotensina-aldosterona (SRAA). El objetivo fue demostrar el efecto antiangiogénico de aliskireno, un DRI, en membranas alantocoriónicas (MAC) de pollo, para lo cual fueron instilados aliskireno y enalapril sobre MAC en distintas concentraciones para realizar su comparación posterior. En secciones histológicas seriadas se registró el número de vasos sanguíneos presentes en 9000 µm2 bajo microscopio de luz a máximo aumento, y se realizó análisis estadístico utilizando ANOVA y el test de Tukey para demostrar posibles diferencias. Los receptores tratados con aliskireno, en ambas concentraciones utilizadas, presentaron menor densidad vascular, en comparación con los controles, siendo ésta estadísticamente significativa a mayor concentración. Aliskireno en concentraciones altas tiene un efecto antiangiogénico en un modelo experimental de MAC. Este hallazgo plantea la necesidad de estudios posteriores, dada la proyección que podría tener el uso inhibidores directos de la renina. A partir de estos resultados, se podría pensar en la factibilidad del uso de aliskireno para la modulación de la angiogénesis en diversas enfermedades crónicas no transmisibles.

Angiogenesis is the formation of new blood vessels from pre-existing ones. Antiangiogenic effect of angiotensin receptor blockers has been reported, however, the relationship between direct renin inhibitors and angiogenesis has not been well described. To assess the antiangiogenic effect of aliskiren, a direct renin inhibitor, on chick embryo chorioallantoic membrane (CAM) assay. Aliskiren and enalapril were instilled in different concentrations and compared. In serial histological sections, the number of blood vessels per 9000 µm2 area under observation through optical microscope using maximum zoom, was registered. Statistical analysis using Anova and Tukey test in order to show possible differences, was performed. Receptors treated with aliskiren presented lower vascular density, which was statistically significant when a higher concentration was administered. High concentrations of aliskiren have an antiangiogenic effect on CAM assay. This finding means further studies are needed, because of the usefulness direct renin inhibitors could have. These results, also, might enhance the possibility of using aliskiren for regulating angiogenesis in the context of non-transmissible chronic diseases.

Simultaneous estimation of Aliskiren hemifumarate and Hydrochlorothiazide in combined Tablet Formulation by Simultaneous equation, Absorbance ratio and First derivative Spectroscopic Methods.

Three simple, sensitive, precise and accurate UV-spectroscopic methods namely simultaneous equation, absorbance ratio and first derivative (zero crossing) spectroscopic methods were developed and validated for simultaneous determination of aliskiren hemifumarate and hydrochlorothiazide in tablet dosage form. Simultaneous equation method was based on the measurement of absorbance at 271 and 280 nm for both the drugs. In absorbance ratio method 255 and 271 nm was used for the quantification of aliskiren hemifumarate and hydrochlorothiazide. First derivative method was involved in the conversion of UV-spectra in to first derivative spectra and measurement of first derivative signal at 241 and 280.2 nm for aliskiren hemifumarate and hydrochlorothiazide, respectively using 2 nm as wavelength interval (Δλ) and 1 as scaling factor. Methods were validated as per ICH guidelines including parameters viz., specificity, linearity and range, precision, accuracy, limit of detection and quantification. All the methods were found to be linear in the concentration range of 6-300 μg/ml for aliskiren hemifumarate and 0.5-25 μg/ml for hydrochlorothiazide. Results of validation studies follows ICH guideline acceptable limits. Methods were compared based on the assay results obtained using one-way ANOVA followed by Bonferroni multiple comparison tests (95% confidence level) as appropriate using computer based fitting program (Prism, Graphpad version 5, Graphpad Software Inc). Results of statistical analysis revealed that there was no significant difference between simultaneous equation, absorbance ratio and first derivative method. Developed methods were simple, rapid, highly sensitive and cost effective as compared to existing methods and can be useful for simultaneous estimation of aliskiren hemifumarate and hydrochlorothiazide in commercial tablet formulation for routine quality control.

Inhibitory effect of aliskiren on LPS-induced angiogenesis of HUVECs / 中国病理生理杂志

AIM:To investigate the inhibitory effect of aliskiren on the angiogenesis of human umbilical vein endothelial cells ( HUVECs) induced by lipopolysaccharide ( LPS) and to explore its possible mechanism.METHODS:HUVECs were cultured and randomly divided into blank group and renin group.The levels of tumor necrosis factor-α(TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in the culture supernatant were detected by ELISA.The protein levels of Toll-like receptor 4 ( TLR4) and ICAM-1 in the HUVECs were determined by Western blot.HUVECs were cul-tured and randomly divided into control group, LPS group, low-dose (1μmol/L) aliskiren group, middle-dose (10μmol/L) aliskiren group and high-dose (100 μmol/L) aliskiren group.The proliferation of HUVECs was detected by MTT and BrdU assays.The mobility of HUVECs was measured by Transwell assay.The formation of the vessels was judged by ob-serving the formation of the luminal structure by HUVECs in Matrigel.The levels of TNF-α, ICAM-1 and monocyte chemo-tactic protein 1 ( MCP-1) in the culture supernatant were measured by ELISA.The expression of renin, TLR4, matrix me-talloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) at mRNA and protein levels in the HUVECs was determined by RT-PCR and Western blot.RESULTS:Renin stimulated the expression of inflammatory factors and TLR4 in the HUVECs.Aliskiren inhibited the growth, migration and angiogenesis of HUVECs in a dose-dependent manner, de-creased the levels of TNF-α, ICAM-1 and MCP-1 and the expression of renin, MMP-2 and MMP-9, and inhibited TLR4 expression (P<0.05).CONCLUSION:Aliskiren inhibits LPS-induced angiogenesis of HUVECs, which may be related to the down-regulation of renin expression, the inhibition of TLR4-mediated inflammatory reaction, and the formation of MMP-9 and MMP-2.

Combined aliskiren and L-arginine treatment has antihypertensive effects and prevents vascular endothelial dysfunction in a model of renovascular hypertension

Angiotensin II is a key player in the pathogenesis of renovascular hypertension, a condition associated with endothelial dysfunction. We investigated aliskiren (ALSK) and L-arginine treatment both alone and in combination on blood pressure (BP), and vascular reactivity in aortic rings. Hypertension was induced in 40 male Wistar rats by clipping the left renal artery. Animals were divided into Sham, 2-kidney, 1-clip (2K1C) hypertension, 2K1C+ALSK (ALSK), 2K1C+L-arginine (L-arg), and 2K1C+ALSK+L-arginine (ALSK+L-arg) treatment groups. For 4 weeks, BP was monitored and endothelium-dependent and independent vasoconstriction and relaxation were assessed in aortic rings. ALSK+L-arg reduced BP and the contractile response to phenylephrine and improved acetylcholine relaxation. Endothelium removal and incubation with N-nitro-L-arginine methyl ester (L-NAME) increased the response to phenylephrine in all groups, but the effect was greater in the ALSK+L-arg group. Losartan reduced the contractile response in all groups, apocynin reduced the contractile response in the 2K1C, ALSK and ALSK+L-arg groups, and incubation with superoxide dismutase reduced the phenylephrine response in the 2K1C and ALSK groups. eNOS expression increased in the 2K1C and L-arg groups, and iNOS was increased significantly only in the 2K1C group compared with other groups. AT1 expression increased in the 2K1C compared with the Sham, ALSK and ALSK+L-arg groups, AT2 expression increased in the ALSK+L-arg group compared with the Sham and L-arg groups, and gp91phox decreased in the ALSK+L-arg group compared with the 2K1C and ALSK groups. In conclusion, combined ALSK+L-arg was effective in reducing BP and preventing endothelial dysfunction in aortic rings of 2K1C hypertensive rats. The responsible mechanisms appear to be related to the modulation of the local renin-angiotensin system, which is associated with a reduction in endothelial oxidative stress.

Bloqueadores do sistema renina-angiotensina em ilhotas pancreáticas e fígado na obesidade induzida por dietas em camundongos / Renin-angiotensin system blockers in pancreatic islets and liver on diet-induced obesity in mice

As associações entre obesidade, doença hepática gordurosa não alcoólica (NAFLD) e diabetes mellitus tipo 2 (DM2) são bem estabelecidas, e o sistema renina-angiotensina (SRA) pode proporcionar uma ligação entre eles. O bloqueio do SRA em diferentes níveis pode estar relacionado a respostas na resistência à insulina, remodelagem do pâncreas e do fígado em um modelo de obesidade induzida por dieta. Camundongos C57BL/6 foram alimentados com uma dieta hiperlipídica (HF) durante oito semanas e depois tratados com alisquireno (50 mg/kg/dia), enalapril (30 mg/kg/dia) ou losartana (10 mg/kg/dia) por um período adicional de seis semanas. As drogas foram incorporadas na dieta. Avaliou-se a massa corporal (MC), pressão arterial, consumo e gasto energético (GE), metabolismo da glicose e lipídico, histopatologia pancreática e hepática, análise hormonal, imunohistoquímica, perfil gênico e/ou proteico do SRA no pâncreas, gliconeogênese hepática, sinalização da insulina, oxidação e acúmulo lipídico. Todos os inibidores do SRA reduziram significativamente o aumento da pressão arterial nos camundongos alimentados com dieta HF. O tratamento com enalapril, mas não alisquireno ou losartana, reduziu o ganho de MC e a ingestão alimentar; aumentou o GE; amenizou a intolerância à glicose e resistência à insulina; melhorou a massa de células alfa e beta; impediu a redução da adiponectina plasmática e restaurou a sensibilidade à leptina. Além disso, o tratamento com enalapril melhorou a expressão proteica nas ilhotas pancreáticas de Pdx1, GLUT2, ECA2 e do receptor Mas. O tratamento com losartana apresentou uma elevação na expressão proteica de AT2R no pâncreas...

The associations between obesity, NAFLD (non-alcoholic fatty liver disease) and diabetes are well established, and the renin–angiotensin system (RAS) may provide a link among them. . The blocking of the RAS at different levels may be related to responses on insulin resistance, remodeling of the pancreas and liver in a model of diet-induced obesity. Mice (C57BL/6) were fed on a high-fat (HF) diet for 8 weeks and then treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for an additional 6 weeks. The drugs were incorporated into the diet. We assessed body mass (BM), blood pressure, energy intake and expenditure (EE), glucose and lipid metabolism, pancreatic and hepatic histopathology, hormonal analysis, immunohistochemistry, the expression profile of genes and/or proteins affecting pancreas RAS, hepatic gluconeogenesis, insulin signaling and lipid oxidation and accumulation. All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated BM gain, increased EE, enhanced the glucose intolerance and insulin resistance; improved the alpha and beta cell mass; prevented the reduction of plasma adiponectin and restored leptin sensibility. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression in the pancreas. In the liver, the enalapril administration improved hepatic steatosis, triglycerides and prevented the increase hepatic protein levels of PEPCK, G6Pase and GLUT2...

Alisquireno: uma nova opção terapêutica na Cardiomiopatia Hipertrófica / Aliskiren: a new therapeutic option in Hypertrophic Cardiomyopathy

Caso clínico de Cardiomiopatia Hipertrófica (CMH), que após a introdução do alisquireno, houve regressão da massa do Ventrículo Esquerdo (VE) com remodelamento do VE à custa do aumento da cavidade do VE, associado à diminuição da espessura de suas paredes, com manutenção da função do VE. Também ocorreu desaparecimento do gradiente intraventricular de repouso, e durante o estresse esse gradiente deixou de ser significativo. A análise do Eletrocardiograma (ECG) evidenciou melhora do padrão de repolarização ventricular. De sorte que o paciente foi liberado para realizar atividade física não competitiva e gradual.

Clinical case of Hypertrophic Cardiomyopathy (HCM) that after the introduction of aliskiren, there was regression of the Left Ventricle (LV) mass with LV remodeling at the expense of increased LV cavity, associated with decreased thickness of its walls, with maintenance of LV function. There was also disappearance of the intraventricular gradient at rest and during stress, this gradient was no longer significant. The Eletrocardiogram (EKG) analysis showed improvement in ventricular repolarization pattern. So that the patient was released for non-competitive and gradual physical activity.

Effects of Information Provided by Pharmacists on Pharmacotherapy / 医薬品情報学

<b>Objective: </b>There are only a few studies evaluating the effects of drug information services on pharmacotherapy.  We, therefore, studied the effects of providing drug information such as the effectiveness and safety of aliskiren on its pharmacotherapeutic efficacy by comparing before versus after drug information provision.<br><b>Methods: </b>Pharmacists provided drug information such as the effectiveness and safety of aliskiren coadministered with either ACE-I (angiotensin converting enzyme inhibitor) or ARB (angiotensin receptor blocker) to physicians and other healthcare professionals.  We compared the number of patients for whom aliskiren was prescribed, the proportion of diabetic patients taking both aliskiren and ACE-I (or ARB), the proportion of patients with low eGFR (estimated glomerular filtration rate), and the proportion of patients with hyperkalemia and related conditions, before versus after providing the drug information to the healthcare professionals.<br><b>Results: </b>The number of patients for whom aliskiren was prescribed decreased.  The proportion of patients taking both aliskiren and ACE-I (or ARB) decreased significantly after providing the drug information (<i>p</i>=0.007).  The proportion of diabetic patients taking both aliskiren and ACE-I (or ARB), the proportion of patients with low eGFR, and the proportion of patients with hyperkalemia also decreased, after providing the drug information.<br><b>Conclusion: </b>This study showed the drug information service to be clinically beneficial, achieving better pharmacotherapy.  Pharmacists should evaluate and provide information on the effectiveness and safety of drugs announced by authorities in a timely manner to achieve optimal patient care.

Effect research of aliskiren on bradykinin and high sensitive C-reactive protein in hypertension patients / 中国医师进修杂志

Objective To explore the value of a novel non-peptide renin inhibitor aliskiren on hypertension patients,and analyze the change of bradykinin (BK) and high sensitive C-reactive protein (hs-CRP).MethodsEighty patients with mild to moderate hypertension were selected.Patients were randomized divided into ramipril group,aliskiren 75 mg/d group,aliskiren 150 mg/d group,aliskiren 300 mg/d group with 20 cases each by random digits table method and received the following types of intervention:ramipril 5 mg/d,aliskiren 75 mg/d,aliskiren 150 mg/d and aliskiren 300 mg/d.Enzyme-linked immunosorbent assay method was used for detecting hs-CRP.Radioimmunoassay method was used for detecting BK.Results After treatment,the levels of BK and hs-CRP in aliskiren 75 mg/d group,aliskiren 150 mg/d group and aliskiren 300 mg/d group [(5.06 ± 1.61),(5.05 ± 1.87),(5.27 ± 1.39) μg/L and (0.38 ± 0.11 ),(0.25 ± 0.05),(0.33 ± 0.11 ) mg/L] were significantly lower than those in ramipril group [ (7.12 ± 1.12) μ g/L,(0.49 ± 0.19) mg/L ] (P＜0.05 ).After treatment,the levels of SBP and DBP had no significant difference among the four groups (P＞0.05).Conclusion Aliskiren has a very good effect in decreasing blood pressure and does not cause the levels of BK and hs-CRP increasing.

Renin inhibitor in hypertension treatment: from pharmacological point of view.

The use of drugs that inhibit the renin-angiotensin system is one of the effective way to intervene in the pathogenesis of cardiovascular and renal disorders, especially in hypertension treatment. The idea of blocking the renin system at its origin by renin inhibitor has existed for more than 30 years. Renin inhibitor supresses the covension of angiotensinogen into angiotensin, and further deacreases the generation of the active peptide angiotensin II. The first generation (enalkiren) and second generation (remikiren) of orally active renin inhibitors were never used clinically because of low bioavailability and weak blood pressure-lowering activity. At present, aliskiren is the first non-peptide orally active renin inhibitor of the third generation to progress to phase III clinical trials and was approved by U.S. Food and Drug Administration (FDA) in March 2007. Aliskiren becomes the first renin inhibitor with indications for the treatment of hypertension in Indonesia, a compounds with improved oral bioavailability, specificity and efficacy. This review summarises the development of oral renin inhibitors, pharmacological aspects, with a focus on aliskiren.

Aliskiren: A new renin inhibitor as anti-hypertensive.

Hypertension or high blood pressure (BP) is usually defined as a systolic BP> 90 mm Hg. It is a serious condition affecting millions of people every year. The prevalence varies with age, race, education and many other variables. Although number of techniques have been employed for control of blood pressure, still a lot needs to be done in this regard. Lifestyle changes (including weight loss, increased physical activity, and decreased salt and alcohol intake) are the first step in treating hypertension. Hypertension is closely linked to the renin-angiotensinaldosterone system (RAAS). Drugs that inhibit renin have been available for many years but have been limited by low potency, bioavailability and duration of action. Aliskiren is the most advanced of a new class of non-peptide, low–molecular weight, orally active inhibitors introduced recently. In healthy subjects, it produces a dose-dependent reduction in plasma renin activity, angiotensin I and II and aldosterone concentrations. In patients with essential hypertension, aliskiren suppresses plasma renin activity and causes dose-related reductions in blood pressure. The safety and tolerability of aliskiren appears to be comparable to angiotensin antagonists and placebo. Aliskiren has, therefore, a considerable promise for the treatment of hypertension and other cardiovascular and renal diseases.

Protective effect of aliskiren on type 2 diabetic nephropathy in db/db mice / 中华肾脏病杂志

Objective To investigate the effect of aliskiren on type 2 diabetic nephropathy in db/db mice.Methods Eight-week old db/db and db/m mice were subjected to right nephrectomy to hasten the development of diabetic nephropathy.At age of 16 weeks,they were divided into four groups:db/m group (normal control),db/db group ( diabetic control),db/db+ A3 group (db/db mice treated with aliskiren 3 mg·kg-1d-1) and db/db+A25 group (db/db mice treated with aliskiren 25 mg kg-1 d-1).Body weight,blood glucose,glycosylated hemoglobin,proteinuria and systolic blood pressure were measured before and after treatment.After treatment,renal histological examination by PAS staining,TGF-β1 and PAI-1 protein by ELISA,expression of ColⅣ and FN protein by immunofluorescence,mRNA expression of TGF-β1,PAI-1,ColⅣ,FN and renin by real time PCR,renin activity and angiotensin Ⅱ level by radioimmunoassay were performed.Results Treatment for 4 weeks of aliskiren at a dose of 25 mg kg-1 d-1 markedly decreased urinary albumin excretion,glomerulosclerosis and suppressed synthesis of TGF-β1,PAI-1,Col Ⅳ,FN without inducing significantl change in systolic blood pressure,compared to those of db/db group (all P＜0.05).Aliskiren also suppressed renin activity and angiotensin Ⅱ level in renal cortex (all P＜0.05).Conclusion Aliskiren protects against type 2 diabetic nephropathy.

The effects of aliskiren on blood nitric oxide and bradykinin in essential hypertension patients / 中国医师进修杂志

ObjectiveTo investigate the effects of aliskiren on blood nitric oxide(NO) and bradykinin (BK) through analyzing the changes of NO, BK and non-dominant arm blood pressure before and after treatment of aliskiren and ramipril. MethodsThe chnical trial was conducted in 67 patients with essential hypertension. After a single-blind period of taking placebo orally once a day for 2 weeks, the patients were divided into different group in accordance with random table, and all patients were consecutively treated with drugs for 8 weeks. The trial uncovered showed that 17 patients were treated with ramipril (5 mg) in control group. Patients in trial group were given aliskiren and were assigned to three subgroups, 300 mg group (300 mg aliskiren, 16 cases), 150 mg group(150 mg aliskiren, 17 cases) and 75 mg group(75 mg aliskiren, 17 cases). The blood NO and BK before and after treatment in two groups were measured by enzyme linked immunosorbent assay and radioimmunoassay method. Non-dominant arm blood pressure was measured by calibration qualified mercury blood pressure instrument before and after treatment. Results The blood NO after treatment of aliskiren 8 weeks in trial group increased significantly than those before treatment [before treatment, the blood NO in 300 mg group, 150 mg group,75 mg group were (44.414 ±5.841 ), (43.496 ± 5.576), (41.037 ± 5.312) μ mol/L, after treatment they were(60.381 ± 6.756), (56.480 ±6.959), (53.766 ±7.276) μmol/L] (P <0.05). After treatment, non-dominant arm blood pressure decreased significantly in trial group (P < 0.05 ), but the blood BK had no significant defference before and after treatment (P >0.05). The blood NO and BK after treatment of ramipril 8 weeks in control group increased significantly than those before treatment [(57.286 ±6.431) μmol/L vs.(39.935 ±6.388)μ mol/L, (7.120 ± 1.015) μg/L vs.(5.232 ± 1.288) μg/L], and meanwhile non-dominant arm blood pressure decreased significantly(P <0.05). ConclusionsAliskiren and ramipril could increase the concentration of NO remarkably. Ramipril has strong effect in increasing the concentration of BK, but aliskiren hasn't effect on BK.