Verapamil directly inhibits aldosterone synthesis by adrenal mitochondria in vitro.
The action of verapamil, a calcium channel blocker, on the last step of aldosterone biosynthesis (transformation of 18-hydroxycorticosterone into aldosterone) was studied using duck adrenal mitochondria in the absence of regulatory factors. Results show that 10(-5) M verapamil inhibits the transformation of 18-hydroxycorticosterone into aldosterone by 52.8%. Moreover, our findings show that verapamil induces only a slight inhibition of respiratory capacity without action on respiratory control and does not displace 18-hydroxycorticosterone from cytochrome P450 11 beta which catalyses the reaction. Thus, this study does not explain the mechanism of inhibition induced by verapamil on the last step of aldosterone synthesis but it is of interest to note, for clinical use, that this inhibition is not linked to regulatory factors of aldosterone production. Since primary hyperaldosteronisms are characterized by their independence vis-á-vis regulatory factors, administration of verapamil may be particularly interesting for treatment of primary hyperaldosteronisms.
Blanchouin-Emeric
N
N
Service de Biochimie Médicale, Faculté de Médecine, Pitié-Salpétrière, Paris, France.
Zenatti
M
M
Defaye
G
G
Aupetit
B
B
D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D004372:Ducks; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D000450:Aldosterone; D014700:Verapamil