Pretreatment With Angiotensin Receptor Blockade Prevents Left Ventricular Dysfunction and Blunts Left Ventricular Remodeling Associated With Acute Myocardial Infarction

Background— This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI). Methods and Results— Sprague-Dawley rats were pretreated with candesartan (10 mg · kg−1 · d−1) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (P<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (P<0.05) by 37% and 28%, and LV chamber dilation was attenuated (P<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47% (P=0.04) and 70% (P=0.002), and constitutive microtubulin increased 260% (P=0.0005) and 111% (P=0.003). Candesartan had no effect on LV tissue endotheli...