1. A competitive ‘mineralocorticoid’ receptor-binding technique has been used to study plasma ‘mineralocorticoid’ activity in normal and hypertensive states. The binding reaction mixture contains the competitor steroids in undiluted plasma, [3H]aldosterone and rat kidney slices. Thus plasma binding and receptor occupancy can be simultaneously considered.
2. Competitor activities relative to that of aldoterone (100%) were: deoxycorticosterone (DOC), 16%; Cortisol, 0·4%; 18-hydroxydeoxycorticosterone (18-OH-DOC), 0·1%; 16β-OH-dehydroepiandrosterone and 16-oxo-androstenediol, inactive. (Binding characteristics for aldosterone and the other steroids tested with the rat receptor were found to be similar to those with receptors in slices from human kidney, obtained at operation.) These steroids and the spironolactone SC14266 were less active in plasma than in buffer, suggesting that they bind significantly to plasma and that this reduces their capacity to occupy the receptors.
3. These competition data also suggest that at normal and even mildly elevated concentrations, Cortisol does, but DOC and 18-OH-DOC do not, contribute significantly to the plasma mineralocorticoid activity. Competitor activity in plasma samples taken at 12.00 hours from normal subjects (upright) was greater than that in those taken at 08.00 hours (supine). This physiological change, corresponding to an increase in aldosterone, was detected even though there was an associated decrease in plasma Cortisol. Competitor activity in plasma from patients with primary aldosteronism was markedly elevated as compared with that of normal subjects. However, an increase in plasma steroids which bind to the mineralocorticoid receptor was not detected in plasma from patients with ‘low-renin essential hypertension’.