Diltiazem and verapamil: Functional antagonism of exogenous noradrenalin and angiotensin II in man

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Abstract
Summary To evaluate the possible functional antagonism of the calcium antagonists diltiazem and verapamil of the sympathetic nervous system and the renin-angiotensin system, their influence on blood pressure, heart rate, plasma catecholamines and renin activity (PRA), and on the reaction of these parameters to exogenous noradrenaline (NA) and angiotensin II, was investigated in 8 normotensive volunteers. Intravenous diltiazem or verapamil caused a sharp, shortlasting decrease in systolic and diastolic blood pressure, with a maximum 1–3 min after injection and a duration of 10–15 min. Even a further infusion of the calcium antagonists was unable to maintain the initial hypotensive effect. The cessation of the hypotensive effect was not due to reflex stimulation of the sympathetic nervous system, as indicated by unchanged plasma NA and adrenaline levels in the case of diltiazem, but was associated with an increase in PRA. During the administration of diltiazem and verapamil, the increase in blood pressure in response to the infusion of NA and angiotensin II was attenuated; the increase in diastolic pressure was mainly affected. The inhibition was more pronounced at the higher infusion rate of NA and angiotensin II. On the basis of these findings it is suggest that the hypotensive activity of calcium antagonists can be at least partly attributed to a reduction in vascular tone which is maintained by the postjunctional action of noradrenaline and angiotensin II.