Aldosterone And The Pathogenesis Of Hypertension

Hypertension remains a major public health problem, affecting up to 20% of the adult population in Western societies. Despite progress in treatment, the rates of blood pressure control remain suboptimal. Hypertension is a heterogeneous disorder, and in the majority of cases, with so-called "essential" hypertension, no clear single identifiable cause is found. Syndromes of excessive mineralocorticoid production or activity are among the important causes of secondary hypertension. Aldosterone is the principal mineralocorticoid in humans, and primary aldosterone excess, when associated with an aldosterone secreting adenoma (Conn's tumor), is amenable to surgical cure. Classically, patient with Conn's tumor present with spontaneous hypokalemia and have a relative excess of aldosterone production with suppression of plasma levels of renin (a proxy for angiotensin II, the major trophic substance regulating aldosterone secretion). This combination of a high aldosterone and a low renin is however more commonly associated with 'nodular hyperplasia' of the adrenal glands, a condition not improved by surgery and variably responsive to the effects of mineralocorticoid antagonists such as spironolactone. Although primary aldosteronism was previously considered to be rare, recent studies have reported prevalence rates of up to 20% among hypertensive patients. This reflects the increasing use of the plasma aldosterone concentration to renin activity ratio (ARR), rather than spontaneous hypokalemia, as a screening tool for aldosteronism. Many patients with high ARR have normokalemia and, although renin activity is low, the level of aldosterone is usually within the normal range. This group of patients may thus include those who were previously classified as having low-renin essential hypertension. Recent data suggest that disturbances in aldosterone metabolism and regulation may not be uncommon in patients with essential hypertension. Thus, relatively high serum aldosterone levels within the reference range in normotensive individuals are associated with a substantially increased risk of developing hypertension, highlighting the potential role for aldosterone in the etiology of essential hypertension. The present review addresses the physiology of aldosterone action and its role in the pathogenesis of hypertension.