Effects of pretreatment with non hypotensive dose of ramiprilat and losartan on myocardial ischemia-reperfusion induced arrhythmias and infarct size in rats

Inhibition of renin angiotensin system represents an important approach in the management of cardiovascular diseases. The aim of this study was to explore the effects of pretreatment with non-hypotensive dose of angiotensin converting enzyme (ACE) inhibitor, ramiprilat and angiotensin type 1 (AT1) receptor blocker, losartan on myocardial infarct size and arrhythmias in a rat model of ischemia-reperfusion injury. Seventy male Wistar rats were divided into five groups. One group received saline as control. Other groups were given 10 mg/kg/day of losartan for one (L-1W) or ten weeks (L-10W) as well as 50 μg/kg/day of ramiprilat for one (R-1W) or ten weeks (R-10W) using a feeding needle. The rats were subjected to 30 minutes occlusion and 120 minutes reperfusion of the left coronary artery. Infarct size was determined using triphenyl tetrazolium chloride staining. Ischemia-induced ventricular arrhythmias were analyzed in accordance with the Lambeth conventions. Myocardial infarct size and the number of ventricular beats were significantly reduced in R-1W group, but the reduction was not significant in L-1W. After increasing the duration of pretreatment to 10 weeks in L-10W group, the infarct size, the number of ventricular beats and the episodes of ventricular tachycardia were significantly decreased. However in R-10W group the reduction of ventricular arrhythmias was not significant Based on the above mentioned results it could be concluded that losartan and ramiprilat, at a nonhypotensive dose, can reduce the induction of arrhythmias and infarct size following myocardial ischemia reperfusion. These drugs appear to act in a time-dependent manner. Therefore, we expected an increased cardiac effect by long-term administration of losartan. However prolonged treatment with ramiprilat reduced its protective effect.