Mineralocorticoid Actions

MINERALOCORTICOID ACTIONS

The principal mineralocorticoid action is enhancement of Na+ reabsorption in the distal convoluted tubule in kidney. There is an associated increase in K+ and H+ excretion. Its deficiency results in decreased maximal tubular reabsorptive capacity for Na+; kidney is not able to retain Na+ even in the Na+ deficient state → Na+ is progressively lost: kidneys absorb water without attendant Na+ (to maintain e.c.f. volume which nevertheless decreases) → dilutional hyponatraemia → excess water enters cells → cellular hydration: decreased blood volume and raised haematocrit. Hyperkalaemia and acidosis accompany. These distortions of fluid and electrolyte balance progress and contribute to circulatory collapse. Thus, these actions make adrenal cortex essential for survival.

Similar action on cation transport is exerted in other tissues also. The action of aldosterone is expressed by gene mediated increased transcription of mRNA in renal tubular cells which directs synthesis of proteins (aldosteroneinduced proteins—AIP). The Na+K+ ATPase of tubular basolateral membrane responsible for generating gradients for movement of cations in these cells is the major AIP (see Fig. 41.3). Synthesis of subunit of amiloride sensitive Na+ channel is also induced. Because of the time taken to induce protein synthesis, aldosterone has a latency of action of 1–2 hours. In addition, aldosterone rapidly induces phosphorylation and activation of amiloride sensitive Na+ channel.

The main adverse effect of excessive mineralocorticoid action is fluid retention and hypertension. The natural and some of the synthetic glucocorticoids have significant mineralocorticoid activity responsible for side effects like edema, progressive rise in BP, hypokalemia and alkalosis. The diuretic induced hypokalemia is aggravated.

Aldosterone has been shown to promote CHF associated myocardial fibrosis and progression of the disease.