The effects of cocaine and metanephrine on the cardiac responses to norepinephrine infusions.
In open-chest, anesthetized dogs, the effects of blocking the neuronal and extraneuronal uptake mechanisms for norepinephrine on the inotropic and chronotropic responses to norepinephrine infusion were studied. Cocaine, a neuronal uptake blocking agent, potentiated and prolonged the inotropic and chronotropic responses. The chronotropic responses were more prolonged than the inotropic responses. Conversely, metanephrine, an extraneuronal uptake blocking agent, neither potentiated nor prolonged the inotropic and chronotropic responses. Hence, it appears that the neuronal uptake mechanism plays a major role in the sympathetic regulation of the heart, but that the extraneuronal uptake mechanism plays only a minor role. A pronounced interaction between the two uptake mechanisms was observed on the tendency to prolong the inotropic and chronotropic responses, such that the effects of combined blockade were much greater than the sum of the effects produced by separate blockade of the individual uptake mechanisms. However, no such interaction was observed with respect to the magnitudes of the responses.
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004285:Dogs; D004837:Epinephrine / Q000031:analogs & derivatives*; D006339:Heart Rate / Q000187:drug effects*; D008676:Metanephrine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*
D008676:Metanephrine; D003042:Cocaine; D009638:Norepinephrine; D004837:Epinephrine