The effects of neuronal uptake blockade on the cardiac responses to sympathetic nerve stimulation and norepinephrine infusion in anesthetized dogs.
In anesthetized dogs, cocaine ( COC ) was administered intravenously in order to block the neuronal uptake of norepinephrine (NE) by the heart. COC had relatively little effect on the magnitudes of the inotropic and chronotropic responses to sympathetic stimulation, but it did prolong the decay times, especially those of the chronotropic responses. The marked prolongation of the decay times of the chronotropic responses indicates that neuronal uptake must be the main mechanism for dissipating the adrenergic transmitter in the sinus node. However, this mechanism appears to be less important in the ventricular myocardium. At all dosage levels, COC increased the overflow of NE into the coronary sinus blood during cardiac sympathetic stimulation. The extraction of exogenously infused norepinephrine by heart tissue varied inversely with the dose of COC , indicating that the extent of neuronal uptake blockade increased with the dose. Nevertheless, NE overflow into the coronary sinus blood after a relatively large dose (5.7 mg/kg) of COC was less than that observed after a much smaller dose (0.5 mg/kg), suggesting that relatively large doses of COC also tend to inhibit the neuronal release of NE. These results indicate that the effects of COC on the cardiac responses to sympathetic stimulation depend on the balance between its influences on the release and dissipation of neurotransmitter in the neuroeffector gap.
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D017981:Receptors, Neurotransmitter; D003042:Cocaine; D009638:Norepinephrine