Valsartan-induced cardioprotection involves angiotensin II type 2 receptor upregulation in dog and rat models of in vivo reperfused myocardial infarction

Abstract Background Cardioprotection with angiotensin II (AngII) type 1 receptor (AT 1 R) blockade was associated with AngII type 2 receptor (AT 2 R) upregulation and activation during in vivo reperfused myocardial infarction (RMI) in dogs, but it is unclear whether this occurs in rats. Methods and results In vivo hemodynamics, left ventricular (LV) function, infarct size, and AT 1 R/AT 2 R protein (immunoblots) after anterior RMI were measured in rats (60 minutes ischemia, 90 minutes reperfusion, n = 30) and dogs (90 minutes ischemia, 120 minutes reperfusion, n = 22) randomized to pretreatment with valsartan (10 mg/kg, intravenously) or vehicle control, and vehicle sham groups. AT 1 R blockade was confirmed by inhibition of AngII pressor responses at the dose used. Compared with dog and rat controls, valsartan decreased infarct size (52 versus 31% and 47 versus 33%, respectively), improved left ventricular ejection fraction (−32 versus −14% and −46 versus −21%, respectively), limited infarct expansion and infarct thinning, and improved diastolic function after RMI. In both species, AT 2 R protein in the infarct zone decreased in controls and increased with valsartan. Sham animals showed no changes. Conclusions AT 1 R blockade with valsartan induces short-term cardioprotection associated with enhanced AT 2 R expression in both dog and rat models of in vivo RMI.