Neuropeptide Y antagonism reduces reflex cutaneous vasoconstriction in humans.
Previous studies have provided evidence of a non-noradrenergic contributor to reflex cutaneous vasoconstriction in humans but did not identify the transmitter responsible. To test whether neuropeptide Y (NPY) has a role, in two series of experiments we slowly reduced whole body skin temperature (TSK) from 34.5 to 31.7 degrees C. In protocol 1, Ringer solution and the NPY receptor antagonist BIBP-3226 alone were delivered intradermally via microdialysis. In protocol 2, yohimbine plus propranolol (Yoh + Pro), Yoh + Pro in combination with BIBP-3226, and Ringer solution were delivered to antagonize locally the vasomotor effects of NPY and norepinephrine. Blood flow was measured by laser Doppler flowmetry (LDF). Mean arterial blood pressure (MAP) was monitored at the finger (Finapres). In protocol 1, cutaneous vascular conductance (CVC) fell by 45%, to 55.1 +/- 5.6% of baseline at control sites (P < 0.05). At BIBP-3226-treated sites, CVC fell by 34.1% to 65.9 +/- 5.0% (P < 0.05; P < 0.05 between sites). In protocol 2, during body cooling, CVC at control sites fell by 32.6%, to 67.4 +/- 4.3% of baseline; at sites treated with Yoh + Pro, CVC fell by 18.7%, to 81.3 +/- 4.4% of baseline (P < 0.05 vs. baseline; P < 0.05 vs. control) and did not fall significantly at sites treated with BIBP-3226 + Yoh + Pro (P > 0.05; P < 0.05 vs. other sites). After cooling, exogenous norepinephrine induced vasoconstriction at control sites (P < 0.05) but not at sites treated with Yoh + Pro + BIBP-3226 (P > 0.05). These results indicate that NPY participates in sympathetically mediated cutaneous vasoconstriction in humans during whole body cooling.
Stephens
Dan P
DP
Department of Physiology, The University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Saad
Adham R
AR
Bennett
Lee Ann T
LA
Kosiba
Wojciech A
WA
Johnson
John M
JM
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects; D003080:Cold Temperature; D004338:Drug Combinations; D005385:Fingers; D006801:Humans; D007552:Isotonic Solutions; D008297:Male; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D012018:Reflex / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D000077331:Ringer's Solution; D012867:Skin / Q000098:blood supply* / Q000294:innervation; D012879:Skin Physiological Phenomena; D012881:Skin Temperature; D013564:Sympathetic Nervous System / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
C092926:BIBP 3226; D004338:Drug Combinations; D007552:Isotonic Solutions; D009478:Neuropeptide Y; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D015016:Yohimbine; D000077331:Ringer's Solution; D001120:Arginine; D011433:Propranolol; D009638:Norepinephrine