RENAL 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY IS ENHANCED BY RAMIPRIL AND CAPTOPRIL

Changes of renal 11 beta-hydroxysteroid dehydrogenase activity may con tribute to variations of sodium excretion by modulating inactivation o f cortisol or corticosterone and thus their access to mineralocorticoi d receptors. Angiotensin-converting enzyme inhibitors enhance sodium e xcretion but by mechanisms still incompletely understood. To test the hypothesis that the angiotensin-converting enzyme inhibitors ramipril and captopril act in part by enhancing renal 11 beta-hydroxysteroid de hydrogenase activity, the effects of these agents in slices of rat ren al outer medulla were examined. Conversion of H-3-corticosterone to H- 3-11-dehydrocorticosterone was 58% greater in tissue from fasted rats than from fed rats (mean +/- SE 2467 +/- 146 vs. 1584 +/- 102 pmol/mg protein h, P < 0.01). Incubation of tissue from fed rats with physiolo gical concentrations of ramiprilat, the active form of ramipril, enhan ced activity (1497 +/- 76) to fasted levels (2323 +/- 120, P < 0.02). Captopril had a similar in vitro effect (1557 +/- 92 to 2109 +/- 116, P < 0.01). Ramipril given in vivo to fed rats also increased activity to fasted levels (1716 +/- 101 to 2737 +/- 396, P < 0.05). Angiotensin II incubated with renal tissue from fasted rats suppressed activity t o fed levels, but this effect was prevented by the presence of ramipri lat. Both ramipril and captopril enhance renal 11 beta-hydroxysteroid dehydrogenase activity, and this effect is only partly explained by li mitation of endogenous angiotensin II production.