A simultaneous radioimmunoassay for aldosterone and its precursors: human plasma levels following the inhibition of converting enzyme, before and after blockade of prostaglandin biosynthesis.

Plasma aldosterone, 18-hydroxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, and deoxycorticosterone were determined in 15 healthy male volunteers (34 +/- 2 years) following the inhibition of converting enzyme with captopril (SQ 14.225), either with or without indomethacin pretreatment. These studies were performed with the aid of a radioimmunological method for the simultaneous determination of the steroids from 1.0 ml of plasma. The procedure involves one extraction and one chromatographic step. Highly sensitive and specific rabbit antisera were raised for all steroids. Precision and accuracy are shown to be equivalent to those of single steroid radioimmunoassays. Without indomethacin pretreatment a constant and significant fall in aldosterone and 18-hydroxycorticosterone plasma levels was obtained after captopril. 18-Hydroxydeoxycorticosterone and corticosterone did not change after inhibition of converting enzyme. Under indomethacin pretreatment all basal steroid levels were significantly reduced. After captopril, aldosterone did not change and 18-hydroxycorticosterone showed a smaller decrease than without indomethacin. 18-Hydroxydeoxycorticosterone and corticosterone increased significantly 1 1/2 hour after captopril. We conclude that indomethacin significantly reduces basal mineralocorticoid production of adrenal zona glomerulosa and fasciculata. Furthermore, the effect of captopril on aldosterone and 18-hydroxycorticosterone is abolished or diminished by inhibition of prostaglandin biosynthesis, but indomethacin does not prevent an augmented secretion of 18-hydroxydeoxycorticosterone and corticosterone.