Scope of Vasodilatory Effects of Calcium Antagonists

Abstract

Specific Ca antagonists of the verapamil, nifedipine, and diltiazem type have become the drugs of choice in the therapy of cardiac hyperkinetic disorders and of vascular hypertonicity (spasms). The specific mechanism of vasodilatation by Ca antagonists was substantiated by electrophysiological, radionuclear and mechanical measurements on rather different types of arterial vasculature, including the systemic resistance vessels, as well as on portal veins. The results indicate that the vasodilator efficacy of these Ca antagonists is mainly based on at least three components: (1) Suppression of the generation of Ca-carried membrane spike potentials; (2) decrease of direct transmembrane supply of activator Ca through potential- or receptor-operated membrane channels, and (3) interference with Ca-triggered intracellular Ca release in an indirect way, in that Ca antagonists block the influx of small amounts of trigger Ca or produce depletion of intracellular Ca stores. In any case, contractile activation practically ceases if transmembrane Ca supply is totally cut off upon addition of Ca antagonists to a Ca-deficient medium.