Prejunctional beta 2-adrenoreceptor blockade reduces nerve stimulation evoked release of endogenous noradrenaline in skeletal muscle in situ.
Prejunctional beta-adrenoceptor-mediated modulation of endogenous noradrenaline (NA) overflow elicited by sympathetic nerve stimulation was studied in blood-perfused canine gracilis muscle in situ. An attempt was made to subclassify these beta-adrenoceptors by comparing the effects of beta 1-selective (metoprolol) and non-selective (propranolol) beta-adrenoceptor blockade. Animals were pre-treated with desipramine and phenoxybenzamine in order to counteract possible influences of neuronal uptake and stimulation-evoked changes in vascular resistance on the diffusion of NA into the blood stream. Metoprolol did not decrease stimulation-evoked NA overflow, as compared with control experiments (-10 and -8%, respectively). However, propranolol reduced stimulation-evoked NA overflow by 30% in metoprolol pre-treated animals (P less than 0.05 vs. control experiments). Both antagonists elevated basal perfusion pressure, suggesting that vascular post-junctional beta 1- as well as beta 2-adrenoceptors are present. Propranolol increased stimulation-evoked vasoconstriction in metoprolol pre-treated animals, indicating that neuronally released NA may activate postjunctional beta 2-adrenoceptors under these experimental conditions. In conclusion, our findings suggest that NA release can be enhanced by activation of prejunctional beta 2-adrenoceptors in vivo.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D008790:Metoprolol / Q000494:pharmacology; D009132:Muscles / Q000098:blood supply / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D008790:Metoprolol; D009638:Norepinephrine