[Arguments for the existence of an endogenous inhibitor of renal Na-K ATPase with steroid structure and natriuretic action].

In order to explain the opposite effect of 6,7-dihydroxylated isomers of 6, 7 - dihydrocanrenone on the urinary sodium and potassium excretion, we have tested the effect of these substances isolated from human urine on the Na(+)-K+ pump from different tissue preparation: rabbit kidney slices as well as NA-K ATPase purified from the kidney. Our results show an inhibition of pump as well as enzyme activity by the 6 beta 7 alpha isomer while the 2 other isomers are either uneffective or slightly stimulating. The 6 beta 7 alpha dihydroxy-6, 7-dihydrocanrenone could be one of the plasma ouabain-like substance incriminated in the pathogenesis of volume-expanded hypertension.

Effect of various 6-dehydro-corticosteroids, 9, 11-dehydro-DOCA and 9 alpha-fluoro-DOCA on the fluxes of sodium and potassium.

The introduction of a double bond at carbons 6 and 7 (6-dehydro-derivatives) of deoxycorticosterone acetate (DOCA), cortisol-21-acetate, 9 alpha-fluorocortisol-21-acetate (9 alpha-F-C-ac) and aldosterone-21-acetate substantially reduces affinity for Type II receptors but not for Type I receptors. Such a modification changes the effect of these steroids on urinary excretion of Na+ and K+. 6-Dehydro-derivatives will thus bind preferentially to receptor Type I inducing the retention of sodium and compete with mineralocorticoids for such receptors.

Identification of biologically active natural spirolactone derivatives in man and animal.

For the first time, the presence of three natural spirolactones hydroxylated at C6C7 (6 alpha, 7 alpha-, 6 beta, 7 alpha- and 6 beta, 7 beta-dihydroxy-6,7-dihydrocanrenone (DHC) is demonstrated in man and in animal urine (rat, dog, sheep), and possibly in the blood. The existence of the fourth isomer 6 alpha, 7 beta- is also possible. Salt-loading in man and the rat results in a decrease in urinary 6 alpha, 7 alpha- and 6 beta, 7 beta-DHC.

Effect of 6-dehydro-DOCA and 6-dehydro-9 alpha-fluorocortisol acetate on the excretion of sodium and potassium in the rat.

Deoxycorticosterone acetate (DOCA) and 9 alpha-fluorocortisol acetate (9 alpha-F-Cac) can be modified by the introduction of a double bond at carbons 6 and 7 (6-dehydro-derivatives). Such a modification markedly changes the effect of the steroids on urinary excretion of Na+ and K+. Since 6-7 reduction of DOCA and 9 alpha-F-Cac substantially reduces affinity for Type II receptors but not Type I receptors, 6-dehydro-derivatives will thus bind preferentially to receptors influencing the retention of sodium (the "mineralocorticoid" or Type I receptor), and compete with mineralocorticoids for such receptors.