Angiotensin administration stimulates renal 11β-hydroxysteroid dehydrogenase activity in healthy men

Abstract

Background. We examined whether acute administration of angiotensin modulates the activity of 11β-hydroxysteroid dehydrogenase (11βHSD), the intracellular enzyme catalyzing the interconversion between the hormonally active cortisol and inactive cortisone. Methods. Twenty-one male healthy subjects were examined after 1 week of a low- and high-salt diet (50 and 200 mmol/day, respectively). Separate infusions of angiotensin I (Ang I) and II (Ang II) were administered, both at rates of 4 and 8 ng/kg/min. The ratios of tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone (THF + allo-THF/THE) and of free cortisol/free cortisone (UFF/UFE) in urine were measured as indices of overall 11βHSD set point and activity of renal 11βHSD type 2, respectively. Glomerular filtration rate (GFR) was measured by constant infusion of 125I-iothalamate. Results. Ang I and Ang II infusion dose-dependently increased mean arterial blood pressure (MAP) and plasma aldosterone, and decreased plasma renin activity (PRA) and GFR at both diets. Ang I and Ang II infusion resulted in a dose-dependent decrease in the excretion of UFF, UFE, and of the UFF/UFE ratio at both diets, without changing the urinary (THF + allo-THF)/THE ratio. Salt restriction did not affect these 11βHSD variables, but was accompanied by a decrease in UFF and UFE excretion. Conclusion. This study suggests that acute angiotensin administration stimulates the activity of 11βHSD type 2 in human kidney. Angiotensin might therefore exert a dual effect on the mineralocorticoid receptor (i.e., an indirect agonistic effect by increasing aldosterone availability and a direct or indirect antagonistic effect by stimulation of renal 11βHSD type 2 activity).