LOSARTAN ATTENUATES MYOCARDIAL ISCHEMIA-INDUCED VENTRICULAR ARRHYTHMIAS AND REPERFUSION INJURY IN SPONTANEOUSLY HYPERTENSIVE RATS

To assess the efficacy of losartan 4-chloro-5-hydroxymethyl-1-[(2'-(1H -tetrazol-5-yl) biphenyl-4-yl)methyl]imidazole, potassium salt), an an giotensin II receptor antagonist, on acute myocardial ischemia, 36 fou r-month-old spontaneously hypertensive rats were used. The animals und erwent 45 min of left coronary artery occlusion and 1 h of reperfusion and were randomly assigned to control and losartan-treated groups (2, 5, and 10 mg/kg, intravenously). Losartan was administered 15 min bef ore ischemia. Electrocardiograms (lead II) were monitored continuously throughout the experiment. To assess the anti-infarct effect of losar tan, the area at risk was determined by methylene blue dye and the inf arct size was determined by nitroblue tetrazolium chloride staining. T he areas of risk and infarct were measured by computerized planimetry, Results demonstrated that the low and intermediate doses (2 and 5 mg/ kg) of losartan significantly decreased the incidence of ventricular f ibrillation and mortality during the ischemic period induced by left c oronary artery occlusion. However, a significant reduction in infarct size, calculated as a percentage of the area at risk, was noted in all three losartan-treated groups (control: 41.5% +/- 5.2%, losartan, 2 m g/kg: 11.2% +/- 5.8%, 5 mg/kg: 8.5% +/- 2.7% and 10 mg/kg: 13.7% +/- 1 .6%). The results suggest that losartan may be useful in the treatment of ventricular arrhythmias induced by acute myocardial infarction and attenuation of reperfusion injury in hypertension. (C) 1997 American Journal of Hypertension, Ltd.