[Effect of nitrates, nitrate-like substances, calcium antagonists and beta-adrenergic receptor blockers on peripheral circulation]

Abstract

The effectiveness of organic nitrates in the therapy of angina pectoris can be explained from their direct relaxing action on vascular smooth muscle. At conventional dosage the most important action of nitrates is a pooling of blood in the large systemic venous capacitance vessels which leads to a decrease of central venous pressure and ventricular filling pressure. The resulting reduction in left ventricular volume lowers, at virtually constant arterial pressure, systolic wall tension and hence myocardial oxygen consumption. Only at higher dosage, is a distinct dilatation of systemic resistance vessels affected. The fundamental action of the "Ca antagonists", i.e. the inhibition of transmembrane calcium influx in the myocardium and the vascular smooth muscle, includes various beneficial effects for the treatment of angina pectoris. The lowering of myocardial oxygen consumption after application of calcium antagonist is mainly due 1. to the decrease in afterload of the left ventricle, caused by the relaxation of peripheral resistance vessels, 2. to the reduction in ventricular preload by a peripheral venodilation. By a direct inhibitory effect on the coronary vascular tone, coronary blood flow at rest in patients with angina pectoris increases. In addition, Ca antagonists are very efficacious in relieving angiospastic angina. The primary mode of action of beta-blocking drugs in angina pectoris affects, in contrast to the peripheral mechanisms of nitrates and Ca antagonists, is on the heart directly. By the reduction in the extent of exercise heart rate, the increase in cardiac output and, hence, the mean arterial pressure is also significantly lower during exercise under beta-blockade. Beta-blockers also depress the contractile state of myocardium. Therefore, the main factors of the myocardial oxygen consumption (mean arterial pressure, size of the left ventricle, contractility and heart rate) may be essentially influenced. By the decrease in heart rate and the longer diastolic period a better myocardial oxygen delivery results. Besides the immediate cardiac effects of beta-adrenergic blockade, a decline in peripheral resistance combined with a fall in blood pressure occur in hypertensive patients during long-term drug administration. Different hypotheses have been proposed in the last years to explain the antihypertensive mode of action of beta-blockers. Some possible mechanisms are discussed.