Mechanism of the inhibitory effect of etomidate on aldosterone production in isolated bovine glomerulosa cells

Summary

THIS study was designed to examinein vitro the effect of etomidate on aldosterone production in bovine glomerulosa cell suspensions. Etomidate, in a dose dependent manner (71-1779 nmol/l), inhibited both basal and angiotensin ll-stimulated aldosterone production by at least 70±3.6% (mean ±standard error, SEM, degrees of freedom, df, = 4), p<0.025. To elucidate the inhibitory mechanism of etomidate we utilized trilostane, an inhibitor of the conversion of pregnenolone to progesterone, and aminoglutethimide, an inhibitor of the conversion of cholesterol to pregnenolone. Aldosterone production was completely suppressed by each inhibitor. Pregnenolone accumulation in trilostanetreated cells fell from 24.2±7.1 nmol/l to 1.9±0.7 nmol/l with the addition of etomidate, p < 0.005. Aldosterone accumulation from corticosterone added to aminoglutethimide-treated cells fell from 38,405 ±2296 pmol/l to 613 + 105 pmol/l in cells incubated with etomidate, p<0.001. Thus, etomidate is a potent inhibitor of aldosterone production, independently inhibiting both the early and late biosynthetic phases. We have also shown that this inhibition is reversible. Since the therapeutic levels of etomidate range from 356 to 1779 nmol/l, these findings emphasize the possible risk of mineralocorticoid deficiency in suspectible patients receiving this compound.