INHIBITION OF SYMPATHETIC CHOLINERGIC VASODILATATION BY A SELECTIVE NPY Y-2 RECEPTOR AGONIST IN THE GRACILIS MUSCLE OF ANESTHETIZED DOGS

Neuropeptide Y (NPY) is known to be co-stored and co-released from sym pathetic nerve terminals, In the cardiovascular system NPY acts on two main receptor subtypes. At the postjunctional or Y-1 receptor NPY cau ses constriction directly in addition to potentiating other vasoconstr ictor agents. NPY acting at the prejuctional, or Y-2, receptor, inhibi ts the release of neurotransmitter from autonomic nerve terminals. Tn these experiments we used the selective Y-2 receptor agonist N-acetyl[ Leu(28), Leu(31)]NPY24-36 to examine the role of NPY in the modulation of sympathetic vascular control in skeletal muscle in anaesthetised d oss. No systemic presser or local constrictor activity was observed in response to N-acetyl[Leu(28), Leu(31)]NPY24-36 administration, theref ore allowing us to examine the neuroinhibitory actions of NPY in the a bsence of direct vascular effects on blood flow, Stimulation of the sy mpathetic nerves to the gracilis muscle engages both sympathetic choli nergic and sympathetic adrenergic fibres and produces an initial vasod ilatation followed by a slower vasoconstriction. Nerve evoked vasodila tation was inhibited by over 50% in the presence of the selective NPY Y-2 agonist N-acetyl[Leu(28), Leu(31)]NPY24-36. This dilatation uas ab olished by atropine, confirming its cholinergic nature. N-Acetyl[Leu(2 8), Leu(31)]NPY24-36 was found to have no effect on nerve evoked vasoc onstriction. The results demonstrate a NPY Y-2-receptor mediated inhib ition of nerve evoked sympathetic cholinergic vasodilatation but not o f sympathetic vasoconstriction. (C) 1998 Elsevier Science B.V.