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EXPERIMENTAL STUDIES

Comparative effects of pretreatment with captopril and losartan on cardiovascular protection in a rat model of ischemia-reperfusion

^a Division of Cardiology, Department of Medicine, University of California at San Francisco, San Francisco, California, USA

Manuscript received May 4, 1999; revised manuscript received September 1, 1999, accepted November 17, 1999.

Reprint requests and correspondence: Dr. William W. Parmley, 1180-Moffitt Hospital, University of California at San Francisco, San Francisco, California 94143-0124

OBJECTIVES

We sought to assess the comparative effects of pretreatment with captopril and losartan on myocardial infarct size and arrhythmias in a rat model of ischemia-reperfusion.

BACKGROUND

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) inhibit the renin-angiotensin system in different ways. However, the comparative effects of pretreatment with ACE inhibitors or ARBs on acute myocardial infarct size and arrhythmias are unknown.

METHODS

We randomly assigned 117 female Sprague-Dawley rats into three groups: group N was the normal control; group C was given 40 mg/kg body weight per day of captopril in drinking water; and group L was given 40 mg/kg per day of losartan in drinking water. After 10 weeks of pretreatment, 25 rats in each group were subjected to 17 min of left anterior descending coronary artery occlusion and 2 h of reperfusion with hemodynamic and electrocardiographic monitoring. Fourteen rats in each group had blood samples drawn and aortic rings removed to study vascular reactivity.

RESULTS

Mortality during ischemia and reperfusion was lower in combined groups L and C than in group N (4.2% vs. 19.2%, p = 0.042). Rats treated with losartan had significantly higher levels of angiotensin II in their plasma. Hemodynamic variables were not significantly different among the three groups. The thresholds of ventricular fibrillation (VF) before occlusion and after reperfusion were significantly higher in groups L and C than in group N (1.99 ± 0.24 and 1.93 ± 0.27 vs. 1.23 ± 0.17 mA, p = 0.04; 2.13 ± 0.25 and 1.78 ± 0.22 vs. 0.95 ± 0.11 mA, p = 0.001). The average episodes of ventricular tachycardia (VT) and VF per rat were significantly less in groups L and C than in group N (0.96 ± 0.2 and 1.2 ± 0.3 vs. 2.8 ± 0.4 mA, p < 0.001). Myocardial infarct size was significantly smaller in groups L and C than in group N (34 ± 3% and 35 ± 3% vs. 44 ± 3%, p = 0.031, 0.043). Endothelium-dependent vasorelaxation induced by a calcium ionophore (A23187) was increased in both groups but was only statistically significant in group C (p = 0.020).

CONCLUSIONS

Losartan and captopril have similar cardiovascular protective effects in a rat model of ischemia-reperfusion. They increased the threshold of VF, decreased mortality and decreased episodes of VT and VF, as well as decreased myocardial infarct size.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   Ang I = angiotensin I   Ang II = angiotensin II   ANOVA = analysis of variance   ARB = angiotensin II receptor blocker   AT1 = angiotensin II Type I receptor   EC50 = half-maximal effective contraction   LAD = left anterior descending coronary artery   LV = left ventricle or ventricular   TTC = triphenyltetrazolium chloride   VF = ventricular fibrillation   VT = ventricular tachycardia

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