Renin, angiotensin and aldosterone system in pathogenesis and management of hypertensive vascular disease

Abstract

The renin angiotensin aldosterone concatenation, via two effector components, angiotensin II and aldosterone, simultaneously regulates (1) body sodium and water content, (2) arterial blood pressure and (3) potassium balance. Renin, secreted in response to stimuli which compromise kidney perfusion, increases plasma angiotensin and this stimulates aldosterone secretion. Vascular tone is regulated by an interaction between angiotensin levels and available (intravascular) sodium ions. The two hormones thus restore sodium balance and arterial pressure, thereby turning off renin release. Potassium homeostasis is maintained by two direct but opposing effects of plasma potassium levels on aldosterone and renin secretion. Derangements of this cybernetic system are involved in the pathogenesis of malignant hypertension, primary and pseudoprimary aldosteronism, renovascular hypertension and oral contraceptive hypertension. Subtler abnormalities in the renal adrenal axis occur in essential hypertension: Three major subgroups exhibit low (27 per cent), normal (57 per cent) or high plasma renin activity (16 per cent). When aldosterone is included, eight different hormonal profiles have been identified. Longitudinal studies indicate that, in contrast to groups with normal and high renin activity, patients with low renin essential hypertension appear to be protected from the development of strokes and heart attacks despite similar hypertension and cardiac enlargement and a higher age. Taken with the observations in malignant hypertension, plasma renin activity emerges as a risk factor predisposing to serious vascular injury. It thus may be a useful guide for determining etiology and prognosis. New therapeutic strategies are also suggested. Patients with low renin activity may not require early treatment whereas it should be diligently applied in those with high renin activity. Moreover, individualized antihypertensive therapy to correct specific derangements in the renin system holds special promise.