Effects of presynaptic alpha-adrenoceptors and neuronal reuptake on noradrenaline overflow and cardiac response.
Using an in situ perfused, innervated rat heart model, we studied the effects of presynaptic alpha-adrenergic and neuronal reuptake inhibition on evoked noradrenaline (NA) overflow and the postsynaptic response by sympathetic ganglion stimulation. NA overflow was significantly increased by neuronal reuptake inhibitors (desipramine and (+)-oxaprotiline) or by alpha-adrenoceptor antagonists (phentolamine and yohimbine), but the inotropic response was augmented only by alpha-antagonists. In the presence of desipramine, nerve stimulation induced a frequency-dependent increase in NA overflow and postsynaptic response, both were enhanced by yohimbine. In the absence of desipramine, however, postsynaptic response was potentiated by yohimbine despite an unchanged (at 2 and 5 Hz) or even reduced NA overflow (at 10 Hz). Thus, this study suggests that NA release and cardiac response are modulated by presynaptic alpha-adrenoceptors, and that the neuronal reuptake modifies the amount of NA overflow but has little effect on the postsynaptic response.
Department of Medicine (RIE), University of Edinburgh, U.K.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine