Effects of intravenous and oral verapamil upon pressor and adrenal steroidogenic responses in normal man

Abstract

Slow channel calcium antagonists inhibit in vitro both vascular smooth muscle contraction and adrenal steroidogenesis. We assessed the effects of one of these drugs, verapamil, upon pressor responses and increments in plasma steroid concentrations to adrenal trophic factors in normal volunteers. Given acutely iv, verapamil in amounts sufficient to produce plasma concentrations of approximately 200 ng/ml significantly blunted the pressor action of angiotensin II in six normal subjects but did not alter increments in plasma aldosterone or cortisol in response to either angiotensin or ACTH compared to paired control studies. When verapamil was given orally (120 mg three times daily for 5 days), the plasma concentrations were equivalent to those after iv administration of the drug in six other volunteers, and verapamil again significantly blunted pressor responses to angiotensin II and norepinephrine. Oral verapamil also blunted the increments in plasma aldosterone to angiotensin and cortisol to ACTH, but did not alter the aldosterone response to ACTH. We conclude that verapamil given either acutely or chronically impaired the action of pressor hormones by a nonspecific action on vascular smooth muscle. When given for a sustained period of time, verapamil also impaired to a moderate degree adrenal steroidogenesis to two trophic factors, suggesting that its adrenal effect is time dependent.