Effect of endothelin-1 and its combination with adenosine on myocardial contractility and myocardial energy metabolism in vivo.
Contradictory results have been reported about the inotropic effects of the vasoconstrictive peptide endothelin-1 (ET-1). In contrast to in vitro experiments, in vivo studies could not demonstrate a positive inotropy of ET-1. It may be possible, that the direct positive inotropic effect of ET-1 observed in in vitro studies is counterbalanced in vivo by an indirect negative inotropy due to its coronar-constrictive effect. This study examined the hemodynamic and inotropic effects of 2500 ng ET-1/kg without and after pretreatment with the vasodilating nucleoside adenosine (0.5, 2.0, 5.0 mg ADO/kg/min). Data were compared with NaCl controls in open-chest rats during and after a 7-min infusion. Besides measurements in the intact circulation isovolumic measurements were carried out for quantification of myocardial contractility independently of peripheral vascular effects. We further examined the effect of ET-1 and its combination with 2.0 mg ADO/kg/min on myocardial high-energy phosphates (ATP, AMP, ADP, creatine phosphate). ET-1 causes a strong and longlasting vasoconstriction (+ 186% v preinfusion values), which is dose-dependently antagonized in part by ADO (+ 109%, + 136%, + 60%). While the maximum of the isovolumic LVSP (peak LVSP) and the corresponding dP/dtmax (peak dP/dtmax) were unchanged with sole ET-1 (peak LVSP: +5%, peak dP/dtmax: -2%), these indexes of myocardial contractility were increased after pretreatment with ADO (peak LVSP: +11%, +13%, +4%; peak dP/dtmax: +9%, +20%, +10%) indicating a positive inotropic effect of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Beyer
M E
ME
Medizinische Klinik, Abt. III, Eberhard-Karls-Universität, Tübingen, Germany.
Nerz
S
S
Kazmaier
S
S
Hoffmeister
H M
HM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D004338:Drug Combinations; D016232:Endothelins / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D004338:Drug Combinations; D016232:Endothelins; D014665:Vasodilator Agents; D000241:Adenosine