Prejunctional beta 2-adrenoceptor-mediated enhancement of noradrenaline release in skeletal muscle vasculature in situ.
Prejunctional beta-adrenoceptor-mediated modulation of sympathetic neurotransmission was studied in desipramine-pretreated canine blood-perfused gracilis muscle. Overflow of endogenous noradrenaline (NA) to venous plasma and vasoconstriction reflect pre- and postjunctional events in this in vivo model. The nonselective beta-adrenoceptor agonist isoprenaline (15 nM in arterial plasma) and the beta 2-selective agonist rimiterol (50 nM) caused similar vasodilatation (35-40% increase in vascular conductance, p less than 0.01), enhancement of nerve stimulation-evoked vasoconstriction (+20-25%, p less than 0.01), and NA overflow (+13%, p less than 0.05). Isoprenaline, 3 nM, evoked vasodilatation but did not alter NA overflow. Blockade of beta 2-adrenoceptors by ICI 118,551 increased basal vascular tone (+9%, p less than 0.01) and reduced nerve stimulation-evoked vasoconstriction (-7%, p less than 0.05), but failed to alter NA overflow significantly (-12%, p = 0.12). ICI 118,551 blocked all responses to the beta-adrenoceptor agonists. Thus, prejunctional beta 2-adrenoceptor-mediated facilitation of sympathetic neurotransmission could be demonstrated in vivo, but the effects were modest. Previous experiments, however, have demonstrated a considerably larger influence of alpha-adrenoceptor-mediated prejunctional modulation in this model. Hence, prejunctional modulation via beta-adrenoceptors appears to be of subordinate importance when compared with the alpha-adrenoceptor-mediated inhibitory mechanism under these physiological conditions.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000098:blood supply*; D009469:Neuromuscular Junction / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D010880:Piperidines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D007545:Isoproterenol; D009638:Norepinephrine