Sharpe N
Department of Medicine, University of Auckland School of Medicine, New Zealand.
J Cardiovasc Pharmacol. 1993;22 Suppl 9:S9-12.
Angiotensin-converting enzyme inhibitors have been extensively studied and established in the treatment of hypertension, heart failure, and ventricular dysfunction. They have various cardiac and vascular protective effects, but the relevant mechanisms of action in these areas remain to be fully understood. Possible effects of converting-enzyme inhibition related to maintenance of normal endothelial function and inhibition of atherosclerosis should be distinguished from effects on myointimal proliferation related to vascular injury and regression of vascular hypertrophy from blood pressure reduction. Experimental animal studies have showed benefit from converting-enzyme inhibition in preventing myointimal proliferation after vascular injury in some species, but no such effect has been shown in clinical studies of restenosis following coronary angioplasty. Laboratory studies have demonstrated a protective effect of converting-enzyme inhibition on endothelial vasomotor function. Further studies have demonstrated prevention of atherosclerosis in hyperlipidemic rabbits and cholesterol-fed cynomolgus monkeys. Possible mechanisms of action apart from blood pressure lowering include inhibition of angiotensin II and other tissue growth factors and accumulation of kinins. These data, among others, provide sufficient rationale for clinical studies to determine whether converting-enzyme inhibitors can reduce atherosclerotic disease and thus widen their application as cardiac and vascular protective agents.
血管紧张素转换酶抑制剂已在高血压、心力衰竭和心室功能障碍的治疗中得到广泛研究和应用。它们具有多种心脏和血管保护作用,但这些作用在这些领域的相关作用机制仍有待充分了解。与维持正常内皮功能和抑制动脉粥样硬化相关的转换酶抑制作用,应与与血管损伤相关的肌内膜增殖作用以及血压降低导致的血管肥厚消退作用区分开来。实验动物研究表明,在某些物种中,转换酶抑制对预防血管损伤后的肌内膜增殖有益,但在冠状动脉成形术后再狭窄的临床研究中未显示出这种效果。实验室研究已证明转换酶抑制对内皮血管舒缩功能具有保护作用。进一步的研究表明,在高脂血症兔子和喂食胆固醇的食蟹猴中可预防动脉粥样硬化。除了降低血压外,可能的作用机制包括抑制血管紧张素 II 和其他组织生长因子以及激肽的蓄积。这些数据等为临床研究提供了充分的理论依据,以确定血管紧张素转换酶抑制剂是否可以减少动脉粥样硬化疾病,从而扩大其作为心脏和血管保护剂的应用范围。