SPECIES-DIVERSITY OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN THE CARDIOVASCULAR-SYSTEM

Mineralocorticoid (MC) receptors are found in classic (e.g., kidney) a nd nonclassic (e.g., heart and aorta) tissues. MC receptor specificity at either site is conferred by the enzyme 11 beta-hydroxysteroid dehy drogenase (11 beta-HSD), which metabolizes glucocorticoids to inactive 11-ketosteroids. Because the heart and vasculature may be target tiss ues for aldosterone, this study was undertaken. Its objectives were to measure 11 beta-HSD at these sites and to compare levels of activity in the atria and ventricles of different species. Toward this end we f irst determined levels of plasma corticosterone (B) and cortisol (F) ( by using radioimmunoassay), in a variety of species, for subsequent co rrelation with cardiac 11 beta-HSD activity. 11 beta-Dehydrogenation o f glucocorticoids was then assayed in ventricles and atria as well as aorta. Tissue homogenates containing 1 to 5 mg protein were incubated for 1 hour in the presence of 1 mu Ci 5 x 10(-9) mol/L tritiated B or tritiated F and 5 x 10(-4) mol/L oxidized nicotinamide adenine dinucle otide phosphate. Steroid separation and quantitation were achieved by using reverse-phase high-performance liquid chromatography coupled to an online radioisotope detector. For species in which B circulates at relatively high concentrations (rat, rabbit, pig), high levels of dehy drogenation of B to 11-dehydrocorticosterone (A) were observed in both atria and ventricles. Overall, cardiac B to A conversion revels corre sponded to between 0.3 and 0.4 pmol A formed/mg protein/hr. 11 beta-HS D activity was also detected in the aorta. In the rat heart, 11-oxored uction of A to B was equivalent to 11-dehydrogenation of B to A, stron gly suggesting that 11 beta-HSD is a bidirectional enzyme possessing b oth 11 beta-dehydrogenase and 11-oxoreductase activities. 11 beta-Dehy drogenation of B was approximately 10 times lower in species in which F is the dominant glucocorticoid (human, ox, horse, dog). No conversio n of F to cortisone (E) was observed in cardiac or aortic homogenates of any species investigated. Thus, 11 beta-HSD activity is present in cardiovascular tissues and appears to be significantly higher in speci es in which B rather than F predominates in plasma. These findings sho w that diversity exists in the activity of this key guardian enzyme in the cardiovascular system of different species.