Inhibition of sympathetic cholinergic vasodilatation by a selective NPY Y2 receptor agonist in the gracilis muscle of anaesthetised dogs.
Neuropeptide Y (NPY) is known to be co-stored and co-released from sympathetic nerve terminals. In the cardiovascular system NPY acts on two main receptor subtypes. At the postjunctional or Y1 receptor NPY causes constriction directly in addition to potentiating other vasoconstrictor agents. NPY acting at the prejunctional, or Y2 receptor, inhibits the release of neurotransmitter from autonomic nerve terminals. In these experiments we used the selective Y2 receptor agonist N-acetyl[Leu28,Leu31]NPY24-36 to examine the role of NPY in the modulation of sympathetic vascular control in skeletal muscle in anaesthetised dogs. No systemic pressor or local constrictor activity was observed in response to N-acetyl[Leu28, Leu31]NPY24-36 administration, therefore allowing us to examine the neuroinhibitory actions of NPY in the absence of direct vascular effects on blood flow. Stimulation of the sympathetic nerves to the gracilis muscle engages both sympathetic cholinergic and sympathetic adrenergic fibres and produces an initial vasodilatation followed by a slower vasoconstriction. Nerve evoked vasodilatation was inhibited by over 50% in the presence of the selective NPY Y2 agonist N-acetyl[Leu28,Leu31]NPY24-36. This dilatation was abolished by atropine, confirming its cholinergic nature. N-Acetyl[Leu28,Leu31]NPY24-36 was found to have no effect on nerve evoked vasoconstriction. The results demonstrate a NPY Y2-receptor mediated inhibition of nerve evoked sympathetic cholinergic vasodilatation but not of sympathetic vasoconstriction.
Mahns
D A
DA
Prince of Wales Medical Research Institute, Sydney, NSW, Australia.
Revington
M L
ML
Runcie
M J
MJ
McCloskey
D I
DI
Potter
E K
EK
D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000819:agonists*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor