Prejunctional β2-Adrenoceptor -Mediated Enhancement of Noradrenaline Release in Skeletal Muscle Vasculature In Situ

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Abstract
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 < 0.01), enhancement of nerve stimulation-evoked vasoconstriction (+ 20-25%, p < 0.01), and NA overflow (+ 13%, p < 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 < 0.01) and reduced nerve stimulation-evoked vasoconstriction (-7%, p < 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.