[Effect of spironolactones on aldosterone synthesis and adrenal metabolism].
The authors study antialdosterones action on several enzymatic systems in subcellular fractions of animal adrenals. They report an inhibition of aldosterone synthesis located at the corticosterone 18 hydroxylation step but also at the following step of oxydation of 18 hydroxycorticosterone into aldosterone (in the duck as well as in the sheep). In contrast, these drugs do not modify the activity of several enzymes not involved in aldosterone biosynthesis. In addition, anti-aldosterones have decoupling action on mitochondrial respiration. This effect, observed by many authors on adrenal mitochondria can be considered as an illustration of competition between two electron transport chains (phosphorylative oxydation and hydroxylation) and not as a toxic effect. These in vitro results are of clinical interest as they are obtained with antialdosterones concentrations similar to that found in plasma of subjects treated with these diuretics and could explain the absence of secondary hyperaldosteronism in these subjects.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D002191:Canrenoic Acid / Q000494:pharmacology; D002192:Canrenone / Q000494:pharmacology; D004372:Ducks; D006900:Hydroxylation; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D012756:Sheep; D013148:Spironolactone / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D002192:Canrenone; D002191:Canrenoic Acid; D013250:Steroid Hydroxylases
Action des spironolactones sur la synthèse de l'aldostérone et sur le métabolisme surrénalien.