Lee J Y, DeBernardis J F
Cardiovascular Discovery Division, Abbott Laboratories, Abbott Park, IL.
Methods Find Exp Clin Pharmacol. 1990 Apr;12(3):213-25.
Vascular contractile effects of postsynaptic alpha 2-adrenergic receptor stimulation are believed to involve transmembrane calcium influx. Although the current knowledge of the alpha 2-receptor response coupling of vascular smooth muscle contractions is still limited, the fundamental mechanism(s) may involve the extracellular calcium utilization process. This is mediated via the alpha 2-receptor operated calcium channel, which can be pharmacologically distinguished from that mediated via the potential-dependent calcium channel. Therefore, vascular selective alpha 2-antagonists may produce vasorelaxation via a calcium inhibitory action that is different from that of the typical calcium channel blockers. The literature on the in vitro isolated vascular tissue models has been reviewed with emphasis on the methodology for study of alpha 2-antagonist-induced vascular relaxation via selective blockade of the alpha 2-receptor-operated calcium channel. The alpha 2-adrenergic receptors, like alpha 1-receptors on vascular smooth muscle, serve an important role in the control of the arterial, as well as the venous tone in experimental animals and humans in relationship to sympathetic and humoral adrenergic activation of the cardiovascular system. Of particular importance is the possibility that alterations in vascular control of alpha 2-adrenergic mechanisms may lead to increased intracellular free calcium concentrations, thereby causing elevated vascular resistance and high blood pressure. This view is consistent with the long held concept that disturbances of cellular calcium metabolism play a primary role in the pathogenesis of various forms of hypertension. Consequently, selective blockade of vascular alpha 2-adrenergic receptors would be a feasible approach for antihypertensive therapy. This type of antihypertensive agent would be expected to exhibit fewer side effects with efficacy, directed towards the etiology of hypertension.
突触后α₂ - 肾上腺素能受体刺激的血管收缩作用被认为涉及跨膜钙内流。尽管目前对血管平滑肌收缩的α₂ - 受体反应偶联的认识仍然有限，但其基本机制可能涉及细胞外钙利用过程。这是通过α₂ - 受体操纵的钙通道介导的，它在药理学上可与电位依赖性钙通道介导的过程区分开来。因此，血管选择性α₂ - 拮抗剂可能通过与典型钙通道阻滞剂不同的钙抑制作用产生血管舒张。本文综述了体外分离血管组织模型的相关文献，重点介绍了通过选择性阻断α₂ - 受体操纵的钙通道来研究α₂ - 拮抗剂诱导血管舒张的方法。α₂ - 肾上腺素能受体与血管平滑肌上的α₁ - 受体一样，在实验动物和人类中，对于在交感神经和体液肾上腺素能激活心血管系统时控制动脉以及静脉张力起着重要作用。特别重要的是，α₂ - 肾上腺素能机制的血管控制改变可能导致细胞内游离钙浓度升高，从而导致血管阻力增加和高血压。这一观点与长期以来的概念一致，即细胞钙代谢紊乱在各种形式高血压的发病机制中起主要作用。因此，选择性阻断血管α₂ - 肾上腺素能受体将是一种可行的抗高血压治疗方法。这类抗高血压药物预计在疗效方面副作用较少，且针对高血压的病因。
