In vivo receptor characterization of neuropeptide Y-induced effects in consecutive vascular sections of cat skeletal muscle.
1. It has been suggested that the vasoconstrictor response to neuropeptide Y (NPY) is located in the microvessels and that it increases with reduced vessel diameter. The aim of the present study was to analyse quantitatively, on the cat gastrocnemius muscle preparation in vivo, the effects of NPY on total regional vascular resistance (RT) and its distribution to large-bore arterial resistance vessels (> 25 microns; Ra,prox), small arterioles (< 25 microns; Ra,micro) and the veins (Rv). Associated effects on capillary pressure (Pc,v) and fluid exchange were also studied. 2. Close-arterially infused NPY (1-32 micrograms kg-1 min-1) caused a dose-dependent, slowly developing vasoconstriction in all three vascular sections, yet with a preferential action in the small arterioles. At 32 micrograms kg-1 min-1, NPY raised RT by 133 +/- 22%, Ra,prox by 94 +/- 15%, Ra,micro by 277 +/- 104% and Rv by 81 +/- 11%. However, the veins (ED50 = 3.9 +/- 1.2 micrograms kg-1 min-1) were more sensitive to NPY than both large-bore arterial vessels (ED50 = 7.7 +/- 1.6) and small arterioles (ED50 = 7.0 +/- 1.4). NPY decreased Pc,v due to an increase in the pre-to post-capillary resistance ratio. 3. Close-arterial infusions of Pro34NPY and peptide YY evoked vasoconstrictor responses which did not differ from the response to NPY. In contrast, the Y2-preferring C-terminal fragments: Ac-[Leu28, Leu31]-NPY (24-36) and NPY(13-36) were without effect in the muscle vascular bed. The selective NPY Y1 receptor antagonist BIBP3226 (100 micrograms kg-1 min-1, i.a.) abolished the vascular response to NPY. 4. The present findings indicate that the vasoconstrictor response to NPY in skeletal muscle is preferentially located in the small arterioles and mediated via the Y1 receptor and, further, that Y2 and Y3 receptors do not play a significant role in the vasoconstrictor response to NPY in cat skeletal muscle. BIBP3226 was found to be an effective NPY antagonist in vivo and to lack agonist activity.
Ekelund
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U
Department of Physiology and Neuroscience, University of Lund, Sweden.
Erlinge
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D
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013562:Sympathectomy; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D014662:Vasoconstrictor Agents; D001120:Arginine