Use of Calcium Antagonists as Monotherapy in the Management of Hypertension

Abstract

A wide variety of drug treatments are available for the management of hypertension. Often, effective therapy is found only through a process of elimination. A more pathophysiologically oriented method of choosing therapy is based on classification of patients into those with low-, normal-, and high-renin hypertension. In the past, for example, diuretics were considered to be the most effective agents for the treatment of low-renin hypertension. Most cases of essential hypertension are characterized by increased vascular resistance. Calcium channel influx is a major determinant of the free intracellular calcium concentration that finally triggers the contractile process of the vascular smooth muscle cell and thereby determines arterial resistance. In man, free calcium concentration in platelets is closely related to the height of systolic and diastolic blood pressure. Vasodilatation produced by the intra-arterial infusion of a calcium channel blocker into the forearm circulation is significantly greater in hypertensive patients than in normotensive subjects, threefold that observed with sodium nitroprusside, and fourfold that found with prazosin. In hypertensive patients, these effects are correlated directly with plasma epinephrine--reflecting sympathoadrenal activity--and inversely with the activity and reactivity of the renin-angiotensin system. In several clinical studies, the decrease in blood pressure following the administration of calcium channel entry blockers was directly correlated to the patient's age and pretreatment blood pressure, and indirectly to the pretreatment plasma renin activity. The effects of these agents are apparently also comparable to the over-all responses achievable with beta blockers and diuretics. In the future, calcium entry blockers may replace diuretics as first-line therapy for older patients and those with low-renin hypertension.