Renal 11 beta-hydroxysteroid dehydrogenase activity is enhanced by ramipril and captopril.
Changes of renal 11 beta-hydroxysteroid dehydrogenase activity may contribute to variations of sodium excretion by modulating inactivation of cortisol or corticosterone and thus their access to mineralocorticoid receptors. Angiotensin-converting enzyme inhibitors enhance sodium excretion 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 dehydrogenase activity, the effects of these agents in slices of rat renal outer medulla were examined. Conversion of 3H-corticosterone to 3H-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 physiological concentrations of ramiprilat, the active form of ramipril, enhanced 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 to fed levels, but this effect was prevented by the presence of ramiprilat. Both ramipril and captopril enhance renal 11 beta-hydroxysteroid dehydrogenase activity, and this effect is only partly explained by limitation of endogenous angiotensin II production.
Riddle
M C
MC
Department of Medicine, Oregon Health Sciences University, Portland 97201-3098.
McDaniel
P A
PA
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D000806:Angiotensin-Converting Enzyme Inhibitors; D014316:Tritium; D000804:Angiotensin II; D002216:Captopril; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D017257:Ramipril; D003345:Corticosterone