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Titolo:
EFFECTS OF ENDOTHELIN-1 AND IRL-1620 ON MYOCARDIAL-CONTRACTILITY AND MYOCARDIAL ENERGY-METABOLISM
Autore:
BEYER ME; SLESAK G; NERZ S; KAZMAIER S; HOFFMEISTER HM;
Indirizzi:
UNIV TUBINGEN,MED KLIN,ABT 3,OTFRIED MULLER STR 10 D-72076 TUBINGEN GERMANY
Titolo Testata:
Journal of cardiovascular pharmacology
, volume: 26, anno: 1995, supplemento:, 3
pagine: 150 - 152
SICI:
0160-2446(1995)26:<150:EOEAIO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
POTENT; ATRIA; HEART;
Keywords:
IRL 1620; ENDOTHELIN(B) RECEPTOR AGONIST; ENDOTHELIN RECEPTORS; CONTRACTILITY; HIGH-ENERGY PHOSPHATES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
M.E. Beyer et al., "EFFECTS OF ENDOTHELIN-1 AND IRL-1620 ON MYOCARDIAL-CONTRACTILITY AND MYOCARDIAL ENERGY-METABOLISM", Journal of cardiovascular pharmacology, 26, 1995, pp. 150-152

Abstract

In contrast to in vitro studies, experiments in intact animals could not detect a positive inotropic effect of endothelin-1 (ET-1). We presumed that the ET-induced direct positive inotropy is antagonized in vivo by an indirect cardiodepressant effect due to a mainly ET,mediated and ET-induced coronary constriction, with consequent myocardial ischemia. To confirm this hypothesis we examined in thoracotomized rats theeffects of a nonselective activation of ET(A) and ET(B) receptors by 1 nmol/kg ET-1 with and without the vasodilator adenosine (2.0 mg/kg/min), and the effects of a selective activation of ET(B) receptors by the ET(B) agonist IRL 1620 (2 nmol/ kg) on myocardial contractility andenergy metabolism (ATP, ADP, AMP). In addition to recordings in the intact circulation, isovolumic measurements (peak LVSP, peak dP/dt(max)) were performed for quantification of myocardial contractility. ET-1 had no positive inotropic effect (peak dP/dt(max) -2% vs. control, n.s.) due to a marked vasoconstriction with a consequent fall in the myocardial ATP content (-17%; p < 0.01). Adenosine antagonized the ET-induced vasoconstriction in part, normalized myocardial energy metabolism (ATP - 7%), and thus unmasked the positive inotropic effect of ET-1 (peak dP/ dt(max) + 20%; p < 0.01). Selective activation of ET(B) receptors by IRL 1620 had only a small vasoconstrictor effect, which did notproduce myocardial ischemia (ATP + 10%; n.s.) and thus caused a positive inotropic effect in vivo (peak dP/dt(max) + 22%; p < 0.01). The positive inotropic effect of ET-1 is not detectable in vivo as its marked, mainly ET(A)-mediated, vaso- and coronary constriction causes myocardial ischemia that thus produces an indirect negative inotropic effect.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 17:29:17