Role of Angiotensin-1-Receptor Blockers In Cardiorenal Disease

Rene   R.   Wenzel

Abstract

Arterial hypertension is one of the most important risk factors for cardiovascular disease. Angiotensin-1- receptor blockers (ARB) are a class of drugs that potently inhibit the vasoconstriction and other vascular effects of angiotensin including proliferation of vascular smooth muscle cells by selective binding to the AT1-receptor. The present review summarizes the most relevant experimental and clinical data on this new class of drugs. ARBs inhibit effects of angiotensin II on the vasoconstriction and proliferation of vascular smooth muscle cells, reduce sympathetic activation, increase bradykinin dependent vasodilator effects and increase Ang(1-7), a metabolite of angiotensin, which has vascular protective properties. ARBs also interfere with the interactions of the renin-angiotensinsystem with both the endothelin-system and the sympathetic nervous system. Under in vivo conditions in men, ARBs have a potent antihypertensive effect and have fewer side effects than any other class of antihypertensives. The available ARBs differ regarding their metabolism, plasma half-life and trough-to-peakratio. Several clinical trials have proven that ARBs are safe and effective in reducing morbidity and mortality in hypertension, diabetic and non-diabetic renal disease, acute myocardial infarction as well as systolic and diastolic heart failure. Importantly, protection from cerebrovascular disease and from cardiovascular disease after stroke is an emerging property of ARBs and is likely to be partially independent from the blood-pressure lowering effects. ARBs, similarly to ACE-inhibitors and in contrast to diuretics, have proven to reduce the incidence on new-onset diabetes, which is likely to be clinically relevant in the chronic treatment of hypertension and cardiac disease. Furthermore, ARBs reduce the incidence of atrial fibrillation in hypertensive patients. The reasons for these beneficial effects of ARBs are discussed and include improvement of endothelial function and renal hemodynamics, reduction in central nervous sympathetic tone, interaction with the endothelin-system and potent reduction of left ventricular hypertrophy. Thus, ARBs are an important new, well tolerated class of cardiovascular drugs, which reduce morbidity and mortality from cardiac, renal and cerebrovascular disease.

Keywords: stroke, antiproliferative, antihypertensive, cerebrovascular events, Diabetic nephropathy, fibrillation

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