Liu Y H, Yang X P, Sharov V G, Sigmon D H, Sabbath H N, Carretero O A
Department of Medicine, Henry Ford Hospital, Detroit, MI 48202-2689, USA.
Hypertension. 1996 Jan;27(1):7-13. doi: 10.1161/01.hyp.27.1.7.
After transient episodes of ischemia, benefits of thrombolytic or angioplastic therapy may be limited by reperfusion injury. Angiotensin-converting enzyme inhibitors protect the heart against ischemia/reperfusion injury, an effect mediated by kinins. We examined whether the protective effect of the angiotensin-converting enzyme inhibitor ramiprilat on myocardial ischemia/reperfusion is due to kinin stimulation of prostaglandin and/or nitric oxide release. The left anterior descending coronary artery of Lewis inbred rats was occluded for 30 minutes, followed by 120 minutes of reperfusion. Immediately before reperfusion rats were treated with vehicle, ramiprilat, or the angiotensin II type 1 receptor antagonist losartan. We tested whether pretreatment with the kinin receptor antagonist Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor indomethacin blocked the effect of ramiprilat on infarct size and reperfusion arrhythmias. In controls, infarct size as a percentage of the area at risk was 79 +/- 3%; ramiprilat reduced this to 49 +/- 4% (P < .001), but losartan had little effect (74 +/- 6%, P = NS). Pretreatment with Hoe 140, NG-nitro-L-arginine methyl ester, or indomethacin abolished the beneficial effect of ramiprilat. Compared with the 30-minute ischemia/120-minute reperfusion group, nonreperfused hearts with 30 minutes of ischemia had significantly smaller infarct size as a percentage of the area at risk, whereas in the 150-minute ischemia group it was significantly larger. This suggests that reperfusion caused a significant part of the myocardial injury, but it also suggests that compared with prolonged ischemia, reperfusion salvaged some of the myocardium. Ventricular arrhythmias mirrored the changes in infarct size. Thus, angiotensin-converting enzyme inhibitors protect the myocardium against ischemia/reperfusion injury and arrhythmias; these beneficial effects are mediated primarily by a kinin-prostaglandin-nitric oxide pathway, not inhibition of angiotensin II formation.
短暂性缺血发作后，溶栓或血管成形术治疗的益处可能会受到再灌注损伤的限制。血管紧张素转换酶抑制剂可保护心脏免受缺血/再灌注损伤，这一作用是由激肽介导的。我们研究了血管紧张素转换酶抑制剂雷米普利拉对心肌缺血/再灌注的保护作用是否归因于激肽刺激前列腺素和/或一氧化氮释放。将近交系Lewis大鼠的左冠状动脉前降支闭塞30分钟，然后再灌注120分钟。在再灌注前即刻，给大鼠分别注射溶媒、雷米普利拉或血管紧张素II 1型受体拮抗剂氯沙坦。我们测试了用激肽受体拮抗剂Hoe 140、一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯或环氧化酶抑制剂吲哚美辛预处理是否会阻断雷米普利拉对梗死面积和再灌注心律失常的影响。在对照组中，梗死面积占危险区域面积的百分比为79±3%；雷米普利拉将其降至49±4%（P<0.001），但氯沙坦几乎没有作用（74±6%，P=无显著性差异）。用Hoe 140、NG-硝基-L-精氨酸甲酯或吲哚美辛预处理可消除雷米普利拉的有益作用。与30分钟缺血/120分钟再灌注组相比，缺血30分钟未进行再灌注的心脏，梗死面积占危险区域面积的百分比明显较小，而在150分钟缺血组中则明显较大。这表明再灌注造成了心肌损伤的很大一部分，但也表明与长时间缺血相比，再灌注挽救了一些心肌。室性心律失常反映了梗死面积的变化。因此，血管紧张素转换酶抑制剂可保护心肌免受缺血/再灌注损伤和心律失常；这些有益作用主要由激肽-前列腺素-一氧化氮途径介导，而非抑制血管紧张素II的形成。
