Comparative dose-effect studies with four C-17-spirosteroidal mineralocorticoid synthesis inhibitors

Interference of three spirolactones and a spiro-oxazolidine with mineralocorticoid biosynthesis in the concentration range of 10(-4)-10(-10) M has been studied in isolated dispersed z. glomerulosa cells. Inhibitory effects on several enzyme activities involved in the late steps of aldosterone synthesis have been determined. Different patterns of enzyme inhibition could be observed for each inhibitor. The points of interference were mostly related to cytochrome P450-C11-activities (i.e. 11 beta-/18-hydroxylation and 18-OH-oxidation).