Species diversity of 11 beta-hydroxysteroid dehydrogenase in the cardiovascular system

Mineralocorticoid (MC) receptors are found in classic (e.g., kidney) and nonclassic (e.g., heart and aorta) tissues. MC receptor specificity at either site is conferred by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which metabolizes glucocorticoids to inactive 11-ketosteroids. Because the heart and vasculature may be target tissues 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 first determined levels of plasma corticosterone (B) and cortisol (F) (by using radioimmunoassay), in a variety of species, for subsequent correlation with cardiac 11 beta-HSD activity. 11 beta-Dehydrogenation of 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 muCi 5 x 10(-9) mol/L tritiated B or tritiated F and 5 x 10(-4) mol/L oxidized nicotinamide adenine dinucleotide 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 dehydrogenation of B to 11-dehydrocorticosterone (A) were observed in both atria and ventricles. Overall, cardiac B to A conversion levels corresponded to between 0.3 and 0.4 pmol A formed/mg protein/hr. 11 beta-HSD activity was also detected in the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)