Inhibition by angiotensin II type 1 receptor antagonist of cardiac phenotypic modulation after myocardial infarction

The purpose of this study was to examine the cardiac phenotype and remodeling after myocardial infarction and the effect of the angiotensin II type 1 (AT1) receptor antagonist (TCV-116) on the gene expression. Myocardial infarction in rats was produced by ligation of the coronary artery. TCV-116 (10 mg/kg/day) was administered orally to rats from 1 day after myocardial infarction. At 1, 2 and 3 weeks after myocardial infarction, blood pressure and heart rate were measured, and the heart was removed. The left ventricle was measured for infarct size and weight, and then the total RNA from the non-ischemic left ventricle was extracted. mRNAs in the non-ischemic left ventricle were measured by Northern blot analysis. The weight of the non-ischemic left ventricle was significantly increased 3 weeks after infarction. This was completely prevented by TCV 116 treatment. mRNA levels for β-myosin heavy chain (β-MHC), atrial natriuretic polypeptide (ANP), collagen types I and III and transforming growth factor-β1 (TGF-β1) in the non-ischemic left ventricle were increased by a factor of 3.0, 6.7, 7.9, 4.0 and 1.4 ( P