Antihypertensive and arterial anticalcinotic effects of calcium antagonists

Abstract

In vascular smooth muscle (as in myocardial fibers), a transmembrane supply of calcium ions is required for active tension development. In consequence, calcium antagonists possess a wide scope of action against practically all types of vasoconstrictor or spastic responses of arterial smooth muscle cells. Calcium antagonists are the drugs of choice for the treatment of coronary, pulmonary, cerebral or mesenteric artery spasms. Other clinically important targets of calcium antagonists are the systemic resistance vessels that rapidly dilate, which explains why calcium antagonists are increasingly used for the treatment of acute hypertensive crises as well as for antihypertensive long-term therapy. In physiologic experiments, calcium antagonists normalize the blood pressure of spontaneously hypertensive rats, neutralize various vasoconstrictor agents (if they act via promotion of transmembrane calcium influx), and greatly reduce the sensitivity of the systemic arteries and arterioles to mechanical stimuli, which can produce additional vasoconstriction, if a rise in intraluminal pressure stretches the vascular wall (Bayliss effect). Calcium antagonists also prevent noxious arterial calcium overload in animals. In the human arterial walls, at an advanced age, pathogenic degrees of calcium accumulation are reached and probably play an important role in both the development of hypertension and of arteriosclerotic lesions. Hypertensive rats exhibit progressive arterial calcium overload that responds well to the calcium antagonists nifedipine, nimodipine, nisoldipine and nitrendipine, as well as to verapamil.