Differential effects of cocaine on the positive inotropic effect of noradrenaline mediated by alpha1- and beta-adrenoceptors in failing human myocardium.
Electrically driven (1 Hz) ventricular trabeculae from explanted failing human myocardium were indirectly examined for the localization of the alpha1-adrenoceptor population and the beta-adrenoceptor population in relation to sympathetic nerve endings. We examined the influence of neuronal uptake blockade by cocaine upon the horizontal position of the concentration-response curves for the inotropic effects exerted by noradrenaline in the presence and absence of appropriate adrenoceptor antagonists. Cocaine shifted the concentration-response curve for alpha1-adrenoceptor stimulation, but not that for beta-adrenoceptor stimulation, to lower concentrations of noradrenaline in a parallel manner. The concentration-response curve for combined adrenoceptor stimulation was shifted by cocaine to lower concentrations of noradrenaline in a nonparallel manner. In explanted allograft heart, cocaine had no effect upon the position of the concentration-response curve to alpha1-adrenoceptor stimulation. The data indicate that in the explanted native hearts the alpha1-adrenoceptor population is located close to or within the synaptic cleft, while the beta-adrenoceptor population remaining in the failing myocardium is located more distantly to the neuronal release sites.
Skomedal
T
T
Department of Pharmacology, University of Oslo, Norway. tor.skomedal@labmed.uio.no
Aass
H
H
Geiran
O
O
Osnes
J B
JB
D000328:Adult; D003042:Cocaine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014662:Vasoconstrictor Agents; D003042:Cocaine; D009638:Norepinephrine