The influence of Ca2+-entry blockers on hemodynamics and coronary blood flow, and its importance for the treatment of angina pectoris

Abstract

The way calcium-entry blocking agents, especially nifedipine, act in angina pectoris, is a complex one and is still not completely understood. Nifedipine, through its profound relaxing effect on vascular smooth muscle tone and its predilective action for certain vascular regions, e.g. the peripheral systemic arteriolar system as well as the large coronary arteries, is especially suitable for the treatment of angina pectoris. On the one hand, nifedipine leads to a significant decrease in afterload by reducing blood pressure and peripheral resistance; this results in a considerable decrease in myocardial oxygen consumption, although heart rate, cardiac output and contractility, due to the rise in sympathetic tone, increase mildly. On the other hand, the direct dilating effect on the coronary arteriolar system, increasing coronary blood flow and by this oxygen delivery, especially also in the poststenotic, ischemic region, is strong enough to counteract an autoregulatory drop in coronary flow brought about by the decrease in oxygen consumption, yet not large enough to lead to a steal phenomenon. In this regard, nifedipine behaves differently from nitroglycerin and beta-blocking agents whose effect is accompanied with a decrease in coronary flow in the poststenotic zone, provoked by a drop in the rate-pressure-product and, in the case of beta-blockers also in contractility, i.e., by the decrease in oxygen consumption (Engel and Lichtlen, 1981). The additional effect on some of the high-grade coronary obstructions, especially the eccentric ones, observed both in patients with stable and unstable angina pectoris, has to be regarded as a supporting, not yet well-defined action. However, in Prinzmetal’s angina, the main action of the calcium blocking agents is to be found solely on the large coronary arteries, releasing the spasm and by this transmural ischemia. This effect, although often observed only after high doses of nifedipine, is so overwhelming that calcium antagonists are regarded as the drugs of choice in this disease, preventing and also interrupting the ischemic attacks. Nevertheless, it should be stressed that due to their different sites of action, nitroglycerin and nifedipine act synergistically in these cases.