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.