Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle.
Sympathetic nerve stimulation (2 min, 2 and 10 Hz) increased perfusion pressure in the blood perfused canine gracilis muscle in situ after pretreatment with atropine, desipramine and beta-adrenoceptor antagonists. This vasoconstriction was accompanied by clear-cut increases in the overflow of endogenous noradrenaline (NA) at both frequencies and, at 10 Hz but not at 2 Hz, also of neuropeptide Y-like immunoreactivity (NPY-LI). The irreversible alpha-adrenoceptor antagonist phenoxybenzamine enhanced the nerve stimulation induced overflows of NA and NPY-LI five- to eightfold and threefold, respectively. The fractional overflows of NA and NPY-LI per nerve impulse were similar in response to the high-frequency stimulation, indicating equimolar release in relation to the tissue contents of the respective neurotransmitter. The maximal vasoconstrictor response elicited by 10 Hz was reduced by about 50% following a dose of phenoxybenzamine which abolished the effect of exogenous NA and the remaining response was more long-lasting. Local i.a. infusion of NPY evoked long-lasting vasoconstriction in the presence of phenoxybenzamine, while the stable adenosine 5(1)-triphosphate (ATP) analogue alpha-beta-methylene ATP was without vascular effects. Locally infused NPY reduced the nerve stimulation evoked NA overflow by 31% (P less than 0.01) at 1 microM in arterial plasma, suggesting prejunctional inhibition of NA release. In conclusion, NPY-LI is released from the canine gracilis muscle upon sympathetic nerve stimulation at high frequencies. There is nerve stimulation evoked vasoconstriction, which is resistant to alpha-adrenoceptor blockade. This may in part be mediated by NPY released together with NA from the sympathetic vascular nerves.
Pernow
J
J
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Kahan
T
T
Hjemdahl
P
P
Lundberg
J M
JM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009132:Muscles / Q000098:blood supply* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009478:Neuropeptide Y; D010643:Phenoxybenzamine; D001285:Atropine; D003891:Desipramine; D009638:Norepinephrine