Effect of etomidate on adrenal function in rats

Etomidate, an imidazole derived hypnotic was applied to rats in order to find out whether repeated treatment with the drug, in doses exceeding those usually given to human, does alter adrenal morphology and function in terms of corticosterone and 11 beta-hydroxyandrostenedione (an androgen of exclusively adrenal origin) production, both in vivo and in vitro. A slight, dose-related decrease of plasma corticosterone and 11 beta-hydroxyandrostenedione was observed from etomidate concentrations 0.3 resp. 1.4 mg kg-1 body weight, respectively. In vitro, corticosterone production was reduced in the groups receiving 0.7 mg of the drug or more. Morphologically, only minute lipid hyperplasia was found after the highest dose of etomidate, associated with a significant increase of relative body weight. Administration of low dose of etomidate (approx. one half of that given usually to human) led to an increase of corticosterone production, indicating the reversibility of such effect. Etomidate did not stimulate enzymic oxidation of 11 beta-hydroxysteroids to the corresponding 11-oxosteroids, as do some blockers of 11 beta-hydroxylase.