EVIDENCE OF ABNORMALITIES IN CORTICOSTEROID SECRETION LEADING TO VOLUME-DEPENDENT HYPERTENSION IN MILAN RATS

We examined corticosteroid secretory patterns and their relation to altered salt and water metabolism in Milan hypertensive and normotensive rats. Hypertensive rats had significantly higher blood pressures, exchangeable sodium (hypertensive, 41.2+/-0.3 mmol.kg(-1); normotensive, 38.4+/-0.03 mmol.kg(-1), P<.001), plasma volume (hypertensive, 5.39+/-0.12 mL.100 g(-1); normotensive, 4.84+/-0.10 mL.100 g(-1), P<.001), and plasma concentrations of atrial natriuretic peptide (hypertensive, 38.8+/-4.0 pg.mL(-1), normotensive, 22.4+/-3.1 pg.mL(-1), P<.02). These features coincide with those of mineralocorticoid-induced hypertension. Adrenal venous secretory rates (picomoles per minute) of corticosterone (hypertensive, 1696+/-202; normotensive, 873+/-139), 18-hydroxycorticosterone (hypertensive, 49.7+/-8.3; normotensive, 25.7+/-3.3), and aldosterone (hypertensive, 1.16+/-0.17; normotensive, 0.52+/-0.08) were higher in the hypertensive than the normotensive strain, but that of 11-deoxycorticosterone (DOC) (hypertensive, 94.4+/-14.9; normotensive, 114.3+/-33.9) was similar in the two strains. The corticosterone-DOC, 18-hydroxycorticosterone-DOC, and aldosterone-DOC ratios were higher in the hypertensive than the normotensive strain (P<.02), but the 18-hydroxycorticosterone-corticosterone and aldosterone-18-hydroxycorticosterone ratios were not. These results indicate increased activity of the ''late'' aldosterone biosynthetic pathway in the hypertensive compared with the normotensive strain caused by an increased conversion rate of DOC to corticosterone. The comparison of corticosterone secretion between the two strains indicates that 11 beta-hydroxylase rather than aldosterone synthase activity is more active in the hypertensive than the normotensive rats.