CARDIAC ANGIOTENSIN-II RECEPTORS - STUDIES ON FUNCTIONAL COUPLING IN SPRAGUE-DAWLEY RATS AND TGR(ALPHA-MHC-HAT(1)) TRANSGENIC RATS

Citation
S. Rosenkranz et al., CARDIAC ANGIOTENSIN-II RECEPTORS - STUDIES ON FUNCTIONAL COUPLING IN SPRAGUE-DAWLEY RATS AND TGR(ALPHA-MHC-HAT(1)) TRANSGENIC RATS, European journal of pharmacology, 330(1), 1997, pp. 35-46
Citations number
63
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
330
Issue
1
Year of publication
1997
Pages
35 - 46
Database
ISI
SICI code
0014-2999(1997)330:1<35:CAR-SO>2.0.ZU;2-3
Abstract
The renin-angiotensin system plays an important role in the pathogenes is of cardiac hypertrophy and chronic heart failure as angiotensin II has been shown to induce cardiac hypertrophy and fibrosis. Besides the se structural alterations, functional effects on cardiomyocytes have b een reported in different mammalian species. Angiotensin II is known t o produce a positive inotropic effect in some species, and differences in atrial and ventricular myocardium have been described. So far, the molecular events which govern angiotensin II-mediated changes in card iac contractility are not completely understood. In order to study the dependency of the angiotensin II-induced positive inotropic effect on receptor density, we examined the effect of angiotensin II on cardiac function in atria, papillary muscles and isolated ventricular cardiom yocytes from adult Sprague-Dawley rats and TGR(alpha MHC-hAT(1)) trans genic rats, which expressed the human angiotensin AT(1) receptor (hAT( 1)) specifically in the heart. In atrial myocardium from adult Sprague -Dawley rats, angiotensin II (30 mu mol/l) produced an AT(1)-mediated positive inotropic effect (38.5% of control), whereas in papillary mus cles and isolated ventricular myocytes, no inotropic response was obse rved. As shown by polymerase chain reaction (PCR) and radioligand bind ing, the human angiotensin AT(1) receptor was exclusively expressed in transgenic animals, which markedly overexpressed the angiotensin AT(1 ) receptor. However, in transgenic rats the positive inotropic effect in atrial preparations was similar to the controls, and neither in pap illary muscles nor in isolated cardiomyocytes the increase in receptor density led to an inotropic effect induced by angiotensin II. These d ata suggest that the existence of functionally uncoupled receptors rat her than the low density of receptors at the ventricular site is respo nsible for the inability of ventricular myocardium to respond to angio tensin II. (C) 1997 Elsevier Science B.V.