Endothelial Dysfunction: Clinical Applicability of Calcium Antagonist Drugs

Abstract

Hypertension and other cardiovascular risk factors (such as hypercholesterolaemia and diabetes mellitus) are known to be associated with endothelial dysfunction but, as yet, there is no specific treatment capable of restoring normal endothelial function. In the absence of specific therapies, however, it is possible to adopt the alternative strategy of administering established and effective antihypertensive agents which additionally maybe capable of modifying or reducing the extent and consequences of underlying endothelial dysfunction. For example, the most obvious manifestation of endothelial dysfunction in hypertension is impairment of nitric oxide dependent vasodilator mechanisms and, as a consequence, a relative enhancement of the responses to vasoconstrictor substances such as noradrenaline, angiotensin II and endothelin 1. It is well recognised that calcium antagonist drugs are capable of attenuating the vasoconstrictor responses to all of these substances (Pasanisi et al. 1985; Kiowski et al. 1991; Ueda et al. 1993). An additional consideration is that calcium antagonist drugs have been shown to have anti-atherosclerotic properties which provide therapeutic potential for beneficially modifying a further manifestation of endothelial dysfunction. To date, however, there is no clear evidence in man that calcium antagonist drugs can control blood pressure, delay the development of atherosclerotic lesions and reduce cardiovascular morbidity and mortality. This current lack of evidence does not necessarily indicate that calcium antagonists are unable to provide such benefits in intact man but instead it may reflect the shortcomings and weaknesses of early treatment regimens with prototype calcium antagonist drugs.