ANGIOTENSIN-II TYPE 1A RECEPTOR IS INVOLVED IN THE OCCURRENCE OF REPERFUSION ARRHYTHMIAS

Background-A growing body of evidence has suggested that the renin-ang iotensin system plays an important role in the development of cardiac hypertrophy induced by hemodynamic overload and left ventricular remod eling alter myocardial infarction, The role of the renin-angiotensin s ystem in ischemia-reperfusion (IR) injury, however, has not been estab lished. Methods and Results-To determine the role of angiotensin II (A ng II) in IR injury, we examined infarct size and arrhythmias after IR using Ang II type 1a receptor (AT1a) knockout mice, The left coronary artery was occluded for 30 minutes followed by reperfusion for 120 mi nutes. There were no significant differences in infarct size between w ild-type and knockout mice determined by dual staining with triphenylt etrazolium chloride and Evans blue dye. The number of ventricular prem ature beats after reperfusion in knockout mice, however, was much less than in wild-type mice. Treatment with a selective AT1 antagonist, CV -11974, before ischemia blocked reperfusion arrhythmias in wild-type m ice but had no effects on infarct size. Conclusions-Ang II may be crit ically involved in the induction of ventricular arrhythmias but not in the determination of infarct size after IR.