Receptor subtypes involved in the action of calcium antagonists.

The vasodilator activity of calcium entry blockers which is generally assumed to underlie their antihypertensive potency is probably located at the level of both potential- and receptor-operated channels in the sarcolemma. Although potential-operated channels probably play a major role, more and more evidence is accumulating to suggest that receptor-operated channels make a significant contribution. The receptors which, upon stimulation, trigger the influx of extracellular calcium ions are alpha-adrenoceptors of both subtypes (alpha 1/alpha 2), although the role of alpha 2-adrenoceptors can be understood more readily than that of the alpha 1-subtype. More recent evidence indicates that vascular angiotensin (ANG) II receptors, when stimulated, also cause an influx of extracellular calcium, which is required for the initiation of vasoconstriction. Conversely, all calcium entry blockers so far developed dose-dependently inhibit the calcium influx triggered by the stimulation of either alpha-adrenoceptors or ANG II receptors. Vascular tone is maintained to a substantial degree by the stimulation of alpha-adrenoceptors (both alpha 1 and alpha 2) by circulating and neuronally released catecholamines, and probably also by ANG II in the vascular wall. It is therefore very likely that calcium entry blockers owe an important part of their vasodilator activity to the inhibition of the influence of alpha-adrenoceptor agonists and ANG II via the mechanisms discussed above. Although conclusive evidence is not yet available, part of the transmembranous calcium influx may be explained by a receptor-operated calcium channel which is triggered by either alpha-adrenoceptors or ANG II receptors.