Wollert K C, Drexler H
Abteilung Kardiologie, Medizinische Hochschule Hannover, Germany.
Am J Cardiol. 1997 Aug 4;80(3A):158A-161A. doi: 10.1016/s0002-9149(97)00473-6.
Angiotensin converting-enzyme (ACE) inhibitors attenuate cardiac hypertrophy and prolong survival in animal models and patients after myocardial infarction (MI). Considering the dual function of the ACE, the therapeutic efficacy of ACE inhibitors after MI implicates the renin-angiotensin system and/or the kallikrein-kinin system in the pathophysiology of postinfarction cardiac remodeling. We evaluated the role of kinins, and their potential contribution to the antiremodeling effects of ACE inhibition in this setting. Rats underwent coronary artery ligation followed by chronic B2 kinin receptor blockade with icatibant (HOE 140). Additional groups of MI rats were treated with the ACE inhibitor lisinopril, alone or in combination with icatibant. B2 kinin receptor blockade enhanced the deposition of collagen (morphometric analysis) in the left ventricular interstitial space after MI, whereas markers of cardiomyocyte hypertrophy (left ventricular weights and prepro-atrial natriuretic factor [ANF] expression) were not affected. Chronic ACE inhibition reduced collagen deposition and cardiomyocyte hypertrophy after MI. The inhibitory action of ACE inhibition on interstitial collagen was partially reversed by B2 kinin receptor blockade. However, B2 kinin receptor blockade did not attenuate the effects of ACE inhibition on cardiomyocyte hypertrophy. In conclusion, kinins inhibit the interstitial accumulation of collagen, but do not modulate cardiomyocyte hypertrophy after MI. Kinins contribute to the reduction of myocardial collagen accumulation by ACE inhibition; however, the effects of ACE inhibition on cardiomyocyte hypertrophy are related to reduced generation of angiotensin II.
血管紧张素转换酶（ACE）抑制剂可减轻动物模型和心肌梗死（MI）患者的心脏肥大并延长生存期。鉴于ACE的双重功能，MI后ACE抑制剂的治疗效果表明肾素-血管紧张素系统和/或激肽释放酶-激肽系统参与了梗死后心脏重塑的病理生理学过程。我们评估了激肽在此过程中的作用及其对ACE抑制抗重塑作用的潜在贡献。大鼠接受冠状动脉结扎，随后用依替巴肽（HOE 140）进行慢性B2激肽受体阻断。另外几组MI大鼠单独或联合依替巴肽接受ACE抑制剂赖诺普利治疗。B2激肽受体阻断增强了MI后左心室间质空间中胶原蛋白的沉积（形态计量分析），而心肌细胞肥大标志物（左心室重量和前心钠素原[ANF]表达）未受影响。慢性ACE抑制可减少MI后的胶原蛋白沉积和心肌细胞肥大。B2激肽受体阻断部分逆转了ACE抑制对间质胶原蛋白的抑制作用。然而，B2激肽受体阻断并未减弱ACE抑制对心肌细胞肥大的作用。总之，激肽可抑制MI后胶原蛋白的间质积聚，但不调节心肌细胞肥大。激肽通过ACE抑制有助于减少心肌胶原蛋白的积聚；然而，ACE抑制对心肌细胞肥大的作用与血管紧张素II生成减少有关。
