Effects of Angiotensin AT1 Receptor Antagonist on Volume Overload-Induced Cardiac Gene Expression in Rats.

Abstract

The present study was undertaken to examine the effects of volume overload on cardiac gene expression and the possible role of angiotensin ATl receptor in such expression. Cardiac volume overload was prepared by abdominal aortocaval shunt in rats. Rats with aortocaval shunt were treated with 1) vehicle, 2) an angiotensin ATi receptor antagonist, CS-866 (10 mg/kg/d), or 3) an angiotensin-converting enzyme inhibitor, temocapril (10 mg/kg/d), for 7 days. Cardiac tissue mRNA was measured by Northern blot analysis with specific probes. Aortocaval shunt not only caused cardiac hypertrophy but also upregulated the gene expression of atrial natriuretic polypeptide, collagen III, and downregulated Cat+. ATPase expression in the left ventricle. These changes were prevented by treatment with CS-866, while temocapril failed to normalize left ventricular Cat+-ATPase expression. Unlike the left ventricle, the significant downregulation of a-myosin heavy chain and transforming growth factor-i93 by aortocaval shunt was observed in the right ventricle, and CS-866 normalized this decreased expression of transforming growth factor-/93. The left and right atria showed increased expression of collagen type I as well as of collagen type III and atrial natriuretic polypeptide, and these increases were more effectively prevented by CS-866 than by temocapril. Thus, the effects of cardiac volume overload on cardiac performance-related gene expression differ between the ventricles and atria. Our results suggest that ATi receptor partially contributed to volume overload-induced changes in cardiac gene expression and that ATi receptor antagonists and angiotensin-converting enzyme inhibitors have different effects in this model of cardiac hypertrophy. (Hypertens Res 1997; 20: 133-142)

Metabolic shifts and myocyte hypertrophy in deflazacort treatment ofmdx mouse cardiomyopathy

“…6,18,19 By contrast, decreased synthesis or expression of ␣-cardiac MHC can result from either volume or pressure loading, where the renin-angiotensin II system mediates hemodynamic loading and compensatory hypertrophy. 25,40,50,56 Current data and other reports therefore support the idea that deflazacort-induced hypertrophy and increased ␣-cardiac MHC occurred largely independent of the renin-angiotensin system. 21,27,35,57 Protection from contraction-induced damage may derive from combined increases in laminin, tau- rine, and bFGF that could stabilize membranes, mediate calcium homeostasis, and protect against peroxidation injury, respectively.…”

“…The ratio of ␣-to ␤-cardiac myosin isoforms can provide an index of oxidative and glycolytic capacity, respectively. 18,19,25,50,57 The ␣-cardiac myosin heavy chain (MHC) distribution and concentration may also change during disease and treatment with glucocorticoids. 12 Proton magnetic resonance spectroscopy (H-NMRS) can detect metabolic changes of disease and treatment.…”

Losartan attenuates phospholipase C isozyme gene expression in hypertrophied hearts due to volume overload

“…In this study, treatment of animals with losartan was found to partially prevent cardiac hypertrophy, which is in agreement with other investigators as well as with other AT 1 receptor antagonists [27][28][29][30][31][32] using this model. While some of these investigators [27,28] also reported attenuation of the increased expression of a number of cardiac genes including atrial natriuretic peptide and collagen types I and III in volume overloaded hearts, the attenuation of cardiac hypertrophy may be related to partial attenuation of some of the PLC isozyme gene expression by the action of losartan.…”

“…While some of these investigators [27,28] also reported attenuation of the increased expression of a number of cardiac genes including atrial natriuretic peptide and collagen types I and III in volume overloaded hearts, the attenuation of cardiac hypertrophy may be related to partial attenuation of some of the PLC isozyme gene expression by the action of losartan. This indicates that RAS is partially involved in inducing cardiac hypertrophy and increases in specific PLC isozyme gene expression.…”

Beneficial Effects of Combined Blockade of ACE and AT 1 Receptor on Intimal Hyperplasia in Balloon-Injured Rat Artery

“…CS-866, [17][18][19] a selective nonpeptide AT 1 receptor antagonist, and temocapril hydrochloride, 20 an ACE inhibitor, were provided by Sankyo Co, Ltd. FR172357, 21,22 a nonpeptide bradykinin B 2 receptor antagonist, was provided as a gift by Fujisawa Pharmaceutical Co, Ltd. These drugs were suspended with 0.5% carboxymethylcellulose.…”