Unconjugated and conjugated urinary 19-nor-deoxycorticosterone glucosiduronate. Elevated levels in essential hypertension.

Abstract

SUMMARY The mlneralcorticoid 19-nor-deoxycorticosterone (19-nor-DOC) is present in the urine of rats and humans in unconjugated and conjugated forms. This study sought to compare levels of unconjugated and conjugated 19-nor-DOC glucosiduronate in essential hypertensive subjects. The essential hypertensive and normal subjects were admitted to a metabolic unit, and plasma and urine were collected at fixed intervals on a fixed-electrolyte intake (Na + , 128 mEq/day, K + , 80 mEq/day). The 19-nor-DOC was purified by chromatography and measured by radioimmunoassay. Unconjugated urinary 19-nor-DOC was elevated in essential hypertensive subjects (195 ± 21 [SE] ng/day; n = 21) compared with levels in normal subjects (118 ± 30 [SE] ng/day; n = 13, p < 0.05). Two essential hypertensive subjects had very high levels (673, 729 ng/day), while levels in seven essential hypertensive subjects were below 118 ng/day. Conjugated 19-nor-DOC glucosiduronate also was elevated in essential hypertensive subjects (950 ± 88 [SE] ng/day; n = 8) compared with levels in normal subjects (680 ± 90 [SE] ng/day; n = 5). Seven of eight essential hypertensive subjects had levels greater than 680 ng/day. The unconjugated and conjugated urinary 19-nor-DOC glucosiduronate levels were positively correlated in both of these groups (rho = 0.82, p < 0.01). Other test results including plasma renin activity, plasma aldosterone levels, aldosterone secretion rates, and plasma and urine electrolyte levels were not different between groups. These results indicate that essential hypertensive subjects have increased 19-nor-DOC excretion, which is reflected by increases in both unconjugated and conjugated glucosiduronate forms. Some essential hypertensive subjects, however, had normal urinary 19-nor-DOC levels, which may reflect the heterogeneity of this disease. sterone (19-nor-DOC) was synthesized more than 40 years ago, 1 and Kagawa and Van Arman 2 subsequently found the sodium-retaining activity of this hormone to be between two and five times that of deoxycorticosterone (DOC) itself. The biological significance of 19-nor-DOC was elucidated by the studies of in rat adrenal regeneration hypertension. As 19-nor-DOC is a potent mineralocorticoid produced by both humans and rats, 4 -7 itFrom the Section