[Direct action of mineralocorticoid antagonists on biosynthesis of aldosterone: comparative activities of several new compounds].
Spironolactone is a diuretic steroid which is capable of blocking the binding of aldosterone to its cytosol receptor at the distal convoluted tubule. In addition, it has been shown that spironolactone is a strong inhibitor of steroidogenesis. More recently, new aldosterone antagonists have been discovered. Some of these compounds are more active than spironolactone in competing with aldosterone and have higher specificity for mineralocorticoid receptors. In this study we compare the direct activity of new antimineralocorticoids (SC 23133, SC 19886, SC 26304, and SC 27169) on aldosterone biosynthesis. Marked differences were found in the activity of these compounds upon steroidogenesis. SC 23133 gave rise to a strong inhibiting activity (90%). This activity was reversible (recovery of spontaneous production occurs 150 min after the end of the administration of SC 23133). SC 19886 totally inhibited aldosterone biosynthesis (95%) in a lasting mean. Conversely, SC 27169 and SC 26304 presented no or weak inhibiting effect. Further experiments showed that SC 27169 was unable to block the stimulation of aldosterone biosynthesis induced by corticotropic peptides, whereas the administration of SC 23133 and SC 19886 totally suppressed the stimulatory effect of ACTH and angiotensin II. Owing to the important stimulation of the renin-angiotensin system induced by antimineralocorticoid treatment, these results suggest that SC 23133 and SC 19886 will exert a higher antinatriuretic activity than SC 27169.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D011283:Pregnenes / Q000494:pharmacology; D011898:Ranidae; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D014704:Veratrum Alkaloids / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D011283:Pregnenes; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D014704:Veratrum Alkaloids; D000804:Angiotensin II; C002604:SC 19886; D013148:Spironolactone; C006286:SC 26304; C031320:SC 27169; D000450:Aldosterone; C016699:prorenone; D000324:Adrenocorticotropic Hormone
Action directe des antagonistes des minéralocorticoïdes sur la biosynthèse de l'aldostérone: activités comparées de plusieurs nouveaux composés.