Prejunctional adrenergic receptors and sympathetic neurotransmission: studies in canine skeletal muscle vasculature in situ.
The effects of sympathetic nerve stimulation were studied in blood perfused canine skeletal muscle in situ. The overflow of NA and vasoconstriction, which represent pre- and postjunctional events in this vascular bed, were frequency-dependent and closely related to each other. Measurements of endogenous NA overflow were compared with a conventional radio-labelling technique using 3H-NA. Nerve stimulation evoked overflow of total radioactivity was recovered almost exclusively as 3H-NA. The relative changes of the nerve stimulation evoked overflow of endogenous NA and 3H-NA were much the same. The reproducibility was better for endogenous NA measurements than for the other two indices of transmitter release. Thus, endogenous NA overflow seems to provide a better measure of NA release. There was a preferential overflow of the newly stored radio-labelled transmitter, in agreement with earlier observations in vitro, showing that there is more than one compartment for NA storage in sympathetic nerve endings. Inhibition of neuronal uptake enhanced the nerve stimulation evoked overflow of NA and prolonged the vasoconstrictor response without influencing its amplitude. This would be consistent with a reduced clearance of the released transmitter without major alterations of the NA concentrations at the neuroeffector junction. Inhibition of prostaglandin synthesis did not influence nerve stimulation evoked NA overflow, suggesting that prostaglandin formation is of little importance for the modulation of NA release in this vascular bed. Postjunctional alpha-adrenoceptors of both subtypes may well contribute to the neurogenic control of vascular tone. Circulating catecholamines seem to be more important with regard to activation of the postjunctional alpha 2-adrenoceptors. Postjunctional beta 2-adrenoceptors are to all appearances activated principally by blood borne catecholamines. There was no evidence in favour of physiologically important neurogenic control of these receptors. Nerve stimulation evoked NA overflow was enhanced by alpha-adrenoceptor antagonists and reduced by alpha-adrenoceptor agonists. The findings lend further support to the suggested physiological role of prejunctional alpha 2-adrenoceptor mediated feed-back inhibition of NA release. There may also be a subset of prejunctional alpha 1-adrenoceptors involved in the modulation of sympathetic neurotransmission. The existence of a prejunctional facilitatory beta 2-adrenoceptor could be demonstrated, as stimulation of beta 2-adrenoceptors enhanced nerve stimulation evoked NA overflow.(ABSTRACT TRUNCATED AT 250 WORDS)
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine / Q000378:metabolism; D009132:Muscles / Q000098:blood supply*; D009411:Nerve Endings / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis; D013564:Sympathetic Nervous System / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011453:Prostaglandins; D009638:Norepinephrine; D004837:Epinephrine