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

doi:10.1016/0022-2828(95)90013-6

Journal of Molecular and Cellular Cardiology

Volume 27, Issue 9, September 1995, Pages 1905-1914

https://doi.org/10.1016/0022-2828(95)90013-6 Get rights and content

Abstract

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<0.01), respectively, 1 week after infarction. There was no increase in a-skeletal actin mRNA at 1 and 2 weeks, but it was increased by a factor of 2.9 (P<0.05) at 3 weeks. On the other hand, there was no change in α-MHC mRNA during the 3 weeks. TCV-116 significantly suppressed the increased gene expression of β-MHC and α-skeletal actin in the non-ischemic myocardium at all time points, and also suppressed the expression of ANP at 2 and 3 weeks. However, TCV-116 failed to inhibit the expression of collagen I and III mRNAS at 1 and 3 weeks. These results show that myocardial infarction causes a rapid shift of myocytes to fetal phenotype and a rapid activation of collagen genes in the non-ischemic myocardium. AT 1 receptor may be responsible for the phenotypic modulation of myocotes following myocardial infarction.

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

Abstract

J Am Coll Cnrdiol

Biochem Biophys Res Commun

J Biol Chem

J Biol Chem

Cell

J Mol Cell Cardiol

J Mol Cell Cardiol

J Am CollCardiol

J Mol Cell Cardiol

Left ventricular failure induced by myocardial infarction. I. Myocyte hypertrophy

Am J Physiol

Antithetical accumulation of myosin heavy chain but not -actin mRNA isoforms during early stages of pressure overload-induced rat cardiac hypertrophy

Circ Res

Regulation of myosin isoenzyme composition in fetal and neonatal rat ventricle by endogenous thyroid hormones

J Biol Cheryl

Effect of enalapril on mortality in severe congestive heart failure. Result3 of the cooperative north Scandinavian enalapril survival study (CONSENSUS)

N Engl J Med

Implication of local angiotensin production of cardiovascular physiology pharmacology

Am J Cardiol

Experimental myocardial infarction in the rats

Am J Pathol

Various rat adult tissues express only major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase mutigenic family

Nucleic Acids Res

Construction of DNA sequences complementary to rat al and a2 collagen mRNA and their use in studying the regulation of type 1 collagen synthesis by 1,25-dihydroxyvitamin D

Biochemistry

Tissue-Specific activation of cardiac angiotensin converting enzyme in experimental heart failure

Circ Res

Neurohumoral response to chronic myocardial infarction in rats

Circulation

Antihypertensive effects of a highly potent and long-acting angiotensin 11 subtype- l-receptor antagonist. (±)-1-(Cyclohexyloxycarbonyloxy)-ethyl 2Ethoxy-l -((2′-(1 H-tetrazol-5-yl)biphenyl-4-yl )methyl )1H-benzimidazole-7-carboxylate(TCV 116), in various hypertensive rats

J Pharmacol Exp Ther

Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload

Fibrosis-induced reduction of endomyocardium in the rat after isoproterenol treatment

Circ Revs

Coronary vascular remodeling and myocardial fibrosis in the rat with renovascular hypertension

Am J Hypertens

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