van Zwieten P A, Timmermans P B, van Heiningen P N
Division of Pharmacotherapy, Faculty of Medicine, University of Amsterdam, The Netherlands.
J Hypertens Suppl. 1987 Dec;5(4):S21-8. doi: 10.1097/00004872-198712004-00005.
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.
钙通道阻滞剂的血管舒张活性通常被认为是其抗高血压效力的基础，这种活性可能存在于肌膜中电位门控通道和受体门控通道两个层面。尽管电位门控通道可能起主要作用，但越来越多的证据表明受体门控通道也起重要作用。受刺激后触发细胞外钙离子内流的受体是两种亚型（α1/α2）的α-肾上腺素能受体，不过α2-肾上腺素能受体的作用比α1-亚型更容易理解。最近的证据表明，血管紧张素（ANG）II受体受刺激时也会引起细胞外钙内流，这是血管收缩起始所必需的。相反，迄今为止开发的所有钙通道阻滞剂都能剂量依赖性地抑制由α-肾上腺素能受体或ANG II受体刺激所触发的钙内流。循环和神经释放的儿茶酚胺对α-肾上腺素能受体（α1和α2）的刺激，以及血管壁中ANG II的刺激，在很大程度上维持着血管张力。因此，钙通道阻滞剂的血管舒张活性很可能很大一部分归因于通过上述机制对α-肾上腺素能受体激动剂和ANG II作用的抑制。尽管尚无确凿证据，但部分跨膜钙内流可能由α-肾上腺素能受体或ANG II受体触发的受体门控钙通道来解释。
