Inhibition by Heparinoid of Aldosterone Biosynthesis in Man1

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Abstract
The hepari-noid (RO1-8307) has been administered for from 2 to 5 days to 3 patients with subsequently proven primary aldosteronism. Patients with this disease are uniquely suited for study of the mechanism by which heparin and heparinoid compounds decrease adrenal production of aldosterone because in them the renin-angiotensin system is severely suppressed. This system, therefore, can be eliminated as a possible site of action of heparinoid. In all 3 patients heparinoid induced large decreases in both excretion and secretion of aldosterone, plasma renin activity remaining undetectable before, during and after administration of the compound. Excretion of 18-hydroxytetrahydro-11-dehydrocorticosterone, as an index of 18-hydroxycorticosterone production, was measured on one patient and was sharply suppressed by heparinoid. Excretion of tetrahydrocorticosterone, initially elevated, did not change. It is concluded that heparinoid acts directly upon the adrenal tumor tissue (and presumably normal adrenal tissue as well) to diminish greatly the biosynthesis of aldosterone. The site of the enzymatic block has not been located, but the data suggest that it occurs after the production of corticosterone and before the production of 18-hydroxycorticosterone.