Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.
Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin "essential" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION.
D000450:Aldosterone / Q000378:metabolism*; D000734:Androstenediols / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D003345:Corticosterone / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D003864:Depression, Chemical; D003900:Desoxycorticosterone / Q000097:blood / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology; D006973:Hypertension / Q000097:blood*; D008901:Mineralocorticoids / Q000097:blood*; D011187:Posture; D051381:Rats; D011956:Receptors, Cell Surface; D013997:Time Factors
D000734:Androstenediols; D008901:Mineralocorticoids; D011956:Receptors, Cell Surface; D003900:Desoxycorticosterone; D000450:Aldosterone; D003345:Corticosterone; D006854:Hydrocortisone