Effects of several catecholamines on sympathetic transmission to the myocardium: role of presynaptic alpha-adrenoceptors.
Effects of several alpha-adrenoceptor agonists on presynaptic alpha-adrenoceptors were evaluated by studying chronotropic responses to cardioaccelerator nerve stimulation in anesthetized dogs. I.v. infusions of norepinephrine (NE), methylnorepinephrine (MNE), epinephrine (E) or phenylephrine (PHE) in desipramine-treated dogs caused significant attenuation of nerve stimulation responses. The inhibitory influence of all these agents could be prevented by prior treatment with phentolamine, but not with haloperidol. Comparisons of relative pressor and presynaptic inhibitory actions of these compounds revealed that in equipressor doses, MNE caused a significantly greater attenuation of nerve stimmulation responses than NE, while PHE had similar pressor and presynaptic inhibitory activity to that of NE. The inhibition of chronotropic responses to nerve stimulation observed following E was significantly greater compared to its relative pressor effect. These results demonstrate the existence of a presynaptic alpha-adrenoceptor mechanism modulating cardiac rate in intact dogs and indicate that the false transmitter MNE may be more potent than NE in imparing neuronal transmission by an action on presynaptic alpha-adrenoceptors.
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D002395:Catecholamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D006220:Haloperidol; D003891:Desipramine; D010646:Phentolamine