Spivack C, Ocken S, Frishman W H
Drugs. 1983 Feb;25(2):154-77. doi: 10.2165/00003495-198325020-00004.
Increased peripheral vascular resistance is the cause of elevated systemic blood pressure in most patients with long standing hypertension. The desired haemodynamic effect in antihypertensive therapy is dilation of the constricted arterioles by a drug that acts directly on the vascular smooth muscle while not affecting the heart or the venous return. Hydralazine, diazoxide and minoxidil act directly on vascular smooth muscle to produce vasodilatation and have been used with variable degrees of success in the long term treatment of hypertension. Their cellular mechanism of dilation is not understood fully, but the ability to chelate certain trace metals required for smooth muscle contraction has been proposed as a possible mechanism of action for these drugs. The calcium antagonists (calcium entry blocking drugs) are a distinct group of compounds that interfere with the normal transmembrane flux of extracellular calcium ions on which vascular tissue depends for contraction or impulse generation. Thus, calcium anti-agonists can reduce the contractile activity of the heart, and promote coronary and systemic vasodilatation. These effects provide the clinical rationale for the use of calcium antagonists in the management of ischaemic heart disease and hypertrophic cardiomyopathy. Since systemic vasodilatation can be expected to reduce elevated arterial blood pressure, interest has focused recently on calcium antagonists in the medical management of systemic hypertension. All the calcium antagonists are able, in low concentrations, to relax the smooth muscle vasculature from coronary, cerebral, mesenteric, and renal arteries. The effects on the myocardium, cardiac impulse tissue, and vascular smooth muscle are different in magnitude, however, depending on the individual agent that is used. Clinical experience in the treatment of hypertension with this class of agents is confined to verapamil, nifedipine, and diltiazem. In this article, the scientific rationale for using calcium antagonists in the treatment of arterial hypertension is explored and the clinical experiences with the different calcium antagonists used in hypertension are reviewed.
大多数长期高血压患者的全身血压升高是外周血管阻力增加所致。抗高血压治疗中理想的血流动力学效应是通过一种直接作用于血管平滑肌而不影响心脏或静脉回流的药物使收缩的小动脉扩张。肼屈嗪、二氮嗪和米诺地尔直接作用于血管平滑肌以产生血管扩张作用，并已在高血压的长期治疗中取得了不同程度的成功。它们扩张血管的细胞机制尚未完全明了，但有观点认为，螯合平滑肌收缩所需的某些痕量金属的能力可能是这些药物的作用机制。钙拮抗剂（钙内流阻滞剂）是一类独特的化合物，它们会干扰细胞外钙离子的正常跨膜通量，而血管组织的收缩或冲动产生依赖于此通量。因此，钙拮抗剂可降低心脏的收缩活性，并促进冠状动脉和全身血管扩张。这些作用为钙拮抗剂用于治疗缺血性心脏病和肥厚型心肌病提供了临床依据。由于预计全身血管扩张可降低升高的动脉血压，因此最近人们将注意力集中在钙拮抗剂用于治疗全身性高血压方面。所有钙拮抗剂在低浓度时都能够使冠状动脉、脑动脉、肠系膜动脉和肾动脉的平滑肌血管舒张。然而，根据所使用的具体药物，它们对心肌、心脏冲动组织和血管平滑肌的作用程度有所不同。使用这类药物治疗高血压的临床经验仅限于维拉帕米、硝苯地平和地尔硫䓬。在本文中，我们探讨了使用钙拮抗剂治疗动脉高血压的科学依据，并回顾了用于高血压治疗的不同钙拮抗剂的临床经验。
