Facilitation of nerve stimulation evoked noradrenaline overflow by isoprenaline but not by circulating adrenaline in the dog in vivo.
The influence of isoprenaline and adrenaline on the overflow of endogenous noradrenaline evoked by sympathetic nerve stimulation was studied in canine blood perfused gracilis muscle in situ. Neuronal uptake was inhibited by desipramine. Local i.a. infusions of isoprenaline enhanced stimulation evoked noradrenaline overflow by 32 +/- 10% (P less than 0.05), indicating the existence of prejunctional facilitatory beta-adrenoceptors. This effect of isoprenaline was not antagonized by beta 1-adrenoceptor blockade and does not seem to be related to the vasodilatation caused by isoprenaline. In a second series of experiments circulating adrenaline levels were raised by i.v. infusions from basal levels of 0.4 +/- 0.2 nM to 1.7 +/- 0.2 and 6.3 +/- 0.6 nM, respectively, in arterial plasma. Adrenaline elicited vasodilatation in the gracilis muscle (19 +/- 3 and 28 +/- 5% increases in vascular conductance, respectively), indicating activation of postjunctional beta 2-adrenoceptors, without influencing nerve stimulation evoked noradrenaline overflow. Thus, our results support the existence of a prejunctional beta 2-adrenoceptor mediated mechanism facilitating noradrenaline release in vivo, but provide no evidence to support the idea that physiologically relevant increases in circulating adrenaline levels enhance noradrenergic neurotransmission in skeletal muscle.
D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine / Q000097:blood* / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine