Effect of angiotensin II on rat renal cortical 11 beta-hydroxysteroid dehydrogenase

Renal 11 beta -hydroxysteroid dehydrogenases (11 beta -HSDs) are subject to modulation by various endogenous factors. 11 beta -HSDs convert glucocorti coids into inactive 11-ketones and thereby determine tissue levels of activ e glucocorticoids and thus the extent of glucocorticoid receptor (GR) and m ineralocorticoid receptor (MR) activation. As such, modulation of the activ ity of renal 11 beta -HSDs may contribute to the cascade of regulatory even ts involved in renal electrolyte water handling. We investigated whether re nal 11 beta -HSDs are modulated by elevated circulating angiotensin II. In rats infused for 2 wk with angiotensin II (250 ng/[kg min] subcutaneously), plasma angiotensin II, aldosterone, and corticosterone were raised 5.1-, 1 0.7-, and 2.3-fold, respectively, compared with control rats. Angiotensin I I infusion raised corticosterone 11 beta -oxidation 1.46- and 1.35-fold in renal cortical proximal and distal tubules (enriched by Percoll centrifugat ion), respectively, but had no effect on 11 beta -HSD1 and 11 beta -HSD2 mR NA levels (semiquantitative reverse transcriptase polymerase chain reaction ), except for distal tubular 11 beta -HSD1 mRNA, which was decreased to 50% . In vitro treatment of freshly isolated tubules with angiotensin II for 45 min prior to assessment of 11 beta -HSD activity showed no direct acute ef fects of angiotensin II on tubular corticosterone 11 beta -oxidation, The e nhanced renal tubular corticosterone 11 beta -oxidation in vivo may partly protect renal GR and MR from elevated plasma corticosterone on angiotensin II infusion.