Evidence for Heterogeneity of Mineralocorticoids in Urine of Patients with Low Renin Essential Hypertension*

Abstract

Mineralocorticoid activity in urine of seven patients with low renin essential hypertension and in five normal subjects was evaluated. Urine was collected during continuous treatment with small doses of dexamethasone, which largely eliminated ACTH-dependent steroids without altering blood pressure. Free (unconjugated) steroids were extracted from urine. Urine was then acidified (pH 1.0) and reextracted for conjugated steroids. Extracts were then fractionated using LH-20 columns and high pressure liquid chromatography. The nine fractions thus obtained were subjected to bioassay in adrenalectomized rats, using a decrease in Na to K ratio as the index of mineralocorticoid activity. Aldosterone appeared in fraction 2, corticosterone in fraction 4,11-deoxycorticosterone in fraction 6, and progesterone in fraction 8. In patients with low renin essential hypertension, free unknown mineralocorticoids were excreted in fraction 5 (cases 1–3), in fraction 6 (cases 1, 2, and 4), in fraction 7 (cases 1 and 4), and in fraction 8 (case 4). Conjugated unknown mineralocorticoids were excreted in fraction 5 (case 3) and in fraction 7 (case 2). Measurable amounts of unknown mineralocorticoid were not found in fractions 1, 2, 3, 4, or 9 nor in the urine of three other cases of low renin essential hypertension. Of five normotensive subjects, only 1 excreted detectable quantities of unknown mineralocorticoid, and that appeared in free form in fraction 5. Four other normal subjects had no detectable unknown mineralocorticoid in any fraction. It is concluded that many patients with low renin essential hypertension excrete abnormal quantities of unknown mineralocorticoids, but not all of them excrete the same unknown mineralocorticoids.