Reduced aldosterone metabolites in hypertension.

Significant quantities of 5 alpha and 5 beta-Ring A-reduced metabolites and several polar cytochrome P-450 dependent hydroxylated neutral metabolites of aldosterone (Aldo) (NMA) are soon present in the kidney during the latent period, prior to the expression of Aldo's effects on Na+ and K+. Their levels in the kidney (a) correlate, in a dose-dependent manner, with the magnitude of physiological responses to Aldo in male rats, (b) are lower in the kidneys of females, which show smaller responses to Aldo than males, (c) are lower in the kidneys of males treated with the anti-mineralocorticoid spironolactone, and (d) their synthesis can be regulated by dietary Na+ and K+. Anti-mineralocorticoids completely inhibit synthesis of 5 alpha-reduced metabolites of Aldo in both kidney and toad bladder and of several of the polar hydroxylated NMA in both liver and kidney. 5 alpha-Reduced metabolites and their 2-hydroxylated derivatives possess significant mineralocorticoid activity and their synthesis is increased in rats fed a low Na+ diet and decreased with a high Na+ diet. We have suggested that their synthesis may play a major role in the expression and/or regulation of the individual renal anti-natriuretic and kaliuretic actions of Aldo.