The control of aldosterone secretion in normal and hypertensive man: Abnormal renin-aldosterone patterns in low renin hypertension

Abstract

The problem of the control of aldosterone release is examined with the objective of evaluating evidence suggesting that unidentified factors may be important in activating aldosterone secretion. Two studies are presented which support the view that changes in aldosterone excretion over the range of physiologic variation can be accounted for by known stimuli. Thus, in 157 studies of sixty-one normal subjects, urinary aldosterone excretion was closely correlated with the simultaneous level of plasma renin activity. These observations suggest a major role for renin, via angiotensin generation, in the control of aldosterone secretion. Progressive sodium deprivation in normal subjects consistently induced a positive potassium balance, often not reflected by changes in plasma potassium. This positive balance appears to explain the disproportionately greater increase in aldosterone secretion with respect to renin occurring during sodium depletion. A double-cycle feedback control system is proposed for simultaneous sodium ion and potassium ion homeostasis by the renin-angiotensin-aldosterone system. In this dual interplay, potassium directly affects both renin and aldosterone whereas sodium balance is regulated via renin-induced changes in aldosterone secretion. Patients with either normal renin or high renin essential hypertension exhibit a normal renin-aldosterone interrelationship. A deflection of this interaction, found in some patients with high renin essential hypertension appears consequent to potassium depletion. In contrast, patients with low renin essential hypertension exhibit perhaps four different abnormal renin-aldosterone patterns. Possible mechanisms include a sodium excess with volume expansion, with or without renal tubular defect, an increased sensitivity of adrenal cortical or vascular receptors to angiotensin, an autonomous aldosterone secretory mechanism, and a primary renal defect in renin secretion. Subtle changes in potassium metabolism may also explain some of the observed renin-aldosterone deviations. With all these possibilities, postulation of unidentified adrenotropic or mineralocorticoid hormones, although not excluded, still requires more positive evidence.