Effects of captopril and losartan on myocardial ischemia-reperfusion induced arrhythmias and necrosis in rats


PHARMACOLOGICAL RESEARCH, vol.45, no.4, pp.257-263, 2002 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 45 Issue: 4
  • Publication Date: 2002
  • Doi Number: 10.1006/phrs.2002.0965
  • Page Numbers: pp.257-263


Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type I (AT(1)) receptor blockers improve ischemia-reperfusion induced arrhythmias and infarct size in several animal models. However, the effects of pretreatment with ACEIs or AT, receptor blockers on acute myocardial infarct size and arrhythmias are controversial. Thus, we sought to assess the comparative effects of pretreatment with ACEI captopril and AT(1)-receptor blocker losartan on myocardial infarct size and arrhythmias in a rat model of ischemia-reperfusion. We randomly assigned 92 male Wistar rats for arrhythmias (n = 60) and necrosis (n = 32) experiments. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion and to produce necrosis, the the left main coronary artery was occluded for 30 min, followed by 120 min of reperfusion. Captoptil (3 mg kg(-1)) and losartan (0.2 and 2 mg kg(-1)) were given intravenously 10 min before occlusion. Captopril reduced the incidences of ventricular fibrillation (VF) and mortality associated with irreversible VR whereas the studied doses of losartan did not. Captopril also decreased the number of ventricular beats on reperfusion. Losartan 2 mg kg(-1) reduced both the number of ventricular premature beats and the incidence of ventricular tachycardia (VT) on reperfusion, while losartan at dose of 0.2 mg kg(-1) had no effect on these arrhythmias. Compared to the control group, both captopril and losartan reduced myocardial infarct size in the rat model of ischemia-reperfusion, but this was statistically significant for captopril only. In this experimental model, although captopril did not reduce the incidence of reperfusion-induced VT, it was more effective than the AT(1)-receptor blocker losartan at preventing mortality associated with irreversible VF and to reduce myocardial infarct size in rat model of ischemia-reperfusion. (C) 2002 Elsevier Science Ltd. All rights reserved.