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)