Plasma mineralocorticoid receptor-binding activity has been assessed by inhibition of specific 3H-aldosterone binding by mineralocorticoid receptors in rat kidney slices. This activity was compared to that predicted from the measured plasma concentration of aldosterone, cortisol, and deoxycorticosterone (DOC), calculated from the measured receptor- and plasma-binding activities of these steroids. Total mineralocorticoid receptor-binding activity in pooled plasma from normal subjects was equivalent to 45 ng/dl of aldosterone, a value similar to that expected (51 ng/dl) from measured aldosterone, cortisol, and DOC concentrations. A similar relationship was also found in 17 individual plasma samples from normal subjects. Mean receptor-binding activity in 23 patients with primary aldosteronism was 112 ng/dl, in good agreement with the value predicted from known steroid concentrations (104 ng/dl). High competitor activity (ca. 500 ng/dl) was also found in plasma from 2 subjects with 17α-hydroxylase deficiency. In pooled plasma from a group of subjects with low-renin essential hypertension (LRHT), receptor-binding activity was not significantly different from normal subjects (58 ng/dl in pooled 8.00 a.m. samples, 50 ng/dl in a 6.00 p.m. pool), in agreement with our previous study which reported similar activity in individual patients with LRHT, in normal subjects, and in patients with normal-renin essential hypertension. The data suggest that marked mineralocorticoid excess is not a prominent feature of LRHT. In one patient with glucocorticoid-responsive hypertension, plasma mineralocorticoid activity was high before treatment (88 ng/dl) and decreased to 31 ng/dl during dexamethasone treatment with an increase to 115 ng/dl when dexamethasone was discontinued. In this patient, plasma levels of aldosterone, cortisol, and DOC together accounted for only 60% of total activity, suggesting that an as yet unidentified steroid may contribute to the mineralocorticoid excess in this syndrome. By contrast, two patients with hypokalemic LRHT and subnormal aldosterone showed lower mineralocorticoid receptor-binding activity than normal subjects (23 ng/dl and 27 ng/dl cf. 45 ng/dl). These results suggest that the radioreceptor assay can identify differences between various syndromes of LRHT, further demonstrating its heterogeneity and indicating the need to study each sub-group in order to define pathogenesis.
|Published - 1980