Vascular effects of calcium antagonists: implications for hypertension and other risk factors for coronary heart disease.

All calcium antagonists (CAs) so far developed are vasodilators, and this property is a most important component of their therapeutic potency in hypertension and angina pectoris. At a cellular level, the specific interaction of CAs with transmembranous calcium fluxes involves both potential and receptor-operated channels, respectively. Both alpha 2 and alpha 1 adrenoceptors when activated with an appropriate agonist can trigger the calcium influx through receptor-operated CA channels, alpha 2 adrenoceptors probably more readily so than alpha 1. More recently, angiotensin II receptors have also been demonstrated to be involved, although moderately, in the influx of calcium ions from the extracellular space. The hemodynamic profile of CAs is characterized by a particular specificity for the resistance vessels and for the coronary arterial system, as a useful basis for their therapeutic effect in hypertension and in angina pectoris. The weak natriuretic activity of CAs, probably the result of a tubular effect in the kidney, counteracts the fluid retention to be expected for vasodilator drugs. Interesting ancillary properties of CAs are their potentially favorable effects on the myocardial and vascular hypertrophy associated with long-standing hypertension, as well as their antiatherogenic activity that so far has only been demonstrated in animal models. Such additional properties are of potential benefit and deserve further research, since most large-scale hypertension trials have shown that vasodilatation and the reduction of elevated blood pressure as such, are probably not sufficient to adequately protect hypertensive patients against coronary events.