Mechanisms of action of calcium antagonists in hypertension

Abstract

Cytosolic free calcium concentrations determine the magnitude of tension development of smooth muscle cells and are pivotal for regulation of vascular smooth muscle tone and systemic vascular resistance. Elevated free calcium concentrations have been found in platelets from hypertensive patients, and platelet free calcium concentration, possibly an index of vascular smooth muscle cell free calcium concentration, correlated with blood pressure in normotensive and hypertensive subjects. Increased systemic vascular resistance in essential hypertension depends on increased calcium influx. Calcium antagonists lower cytosolic free calcium concentrations mainly through a reduction of transmembraneous calcium influx and are potent arterial vasodilators. High blood pressure is lowered through a reduction of elevated systemic vascular resistance but, in contrast to other direct acting vasodilators, without clinically relevant sympathetic reflex activation. However, subtle changes of sympathetic nervous system activity may codetermine the acute and chronic blood pressure response. Calcium antagonists do not lead to volume retention, because of improved intrarenal hemodynamics and a diuretic effect. Interference with angiotensin and sympathetically mediated vasoconstrictor mechanisms probably also contributes to their antihypertensive effects. This favorable hemodynamic profile renders calcium antagonists suitable for monotherapy of uncomplicated hypertension where they are particularly effective in older patients and also for the therapy of hypertensive crisis.