1lβ-Hydroxysteroid Dehydrogenase in Vascular Smooth Muscle and Heart: Implications for Cardiovascular Responses to Glucocorticoids*

Publisher Website
Google Scholar
Abstract
The enzyme 11β-hydroxysteroid dehydrogenase (11β-OHSD) converts the active glucocorticoid corticosterone to inactive 11-dehydrocorticosterone in the rat (or cortisol to cortisone in man), thereby protecting renal mineralocorticoid receptors from corticosterone or cortisol and allowing preferential access for aldosterone. We have previously demonstrated that cortisol-induced cutaneous vasoconstriction in man is potentiated by the 11β-OHSD inhibitor glycyrrhetinic acid, suggesting that 11β-OHSD may protect vascular corticosteroid receptors. In this study we report quantitation of 11β-OHSD bioactivity in homogenates of rat aorta, mesenteric artery, caudal artery, and heart, expressed as the percent in vitro conversion of 3H-corticosterone to 3H-ll-dehydrocorticosterone. Nicotinamide adenine dinucleotide phosphate (NADP+)-dependent 11β-OHSD activity was found in all of these tissues and was significantly higher in resistance vessels than aorta (P < 0.05) [without NADP+: caudal artery (4.2 ± 0.2%) = mesenteric artery (2.5 ± 0.7%) = heart (1.67 ± 0.2%) = aorta (0.79 ± 0.2%); with 200 nM NADP+: caudal artery (43.9 ± 2.1%) > heart (20.6 ± 1.0%) = mesenteric artery (17.7 ± 3.1%) = aorta (11.4 ± 0.4%); heart > aorta]. All of these were lower than renal cortex (29.4 ± 1.8% without NADP+; 82.4 ± 0.4% with NADP+; P < 0.001). 3H-11- dehydrocorticosterone was the major metabolite of 3H-corticosterone (>97% of 3H-corticosterone metabolized). Reduction of 3H-ll-dehydrocorticosterone to 3H-corticosterone was not detected in these experiments. We also report localization of 11β- OHSD-like immunoreactivity by immunohistochemistry using antisera raised against rat liver 11β-OHSD, and of 11β-OHSD messenger RNA expression by in situ hybridization using complementary RNA probes transcribed from complementary DNA encoding rat liver 11β-OHSD. We found 11β-OHSD immunoreactivity and messenger RNA expression in vascular and cardiac smooth muscle cytoplasm but not in endothelium. Thus, 11β-OHSD is appropriately sited to modulate access of corticosterone to vascular receptors and could influence vascular resistance, cardiac output and thereby blood pressure. (Endocrinology129: 3305–3312, 1991)

This publication has 0 references indexed in Scilit: