Abstract
Effects of several α-adrenoceptor agonists on presynaptic α-adrenoceptors were evaluated by studying chronotropic responses to cardioaccelarator 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 stimulation 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 presynaptic α-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 α-adrenoceptors.
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