title: VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans.
abstract: Vasoactive intestinal peptide (VIP) is implicated in cutaneous active vasodilation in humans. VIP and the closely related pituitary adenylate cyclase activating peptide (PACAP) act through several receptor types: VIP through VPAC1 and VPAC2 receptors and PACAP through VPAC1, VPAC2, and PAC1 receptors. We examined participation of VPAC2 and/or PAC1 receptors in cutaneous vasodilation during heat stress by testing the effects of their specific blockade with PACAP6-38. PACAP6-38 dissolved in Ringer's was administered by intradermal microdialysis at one forearm site while a control site received Ringer's solution. Skin blood flow was monitored by laser-Doppler flowmetry (LDF). Blood pressure was monitored noninvasively and cutaneous vascular conductance (CVC) calculated. A 5- to 10-min baseline period was followed by approximately 70 min of PACAP6-38 (100 microM) perfusion at one site in normothermia and a 3-min period of body cooling. Whole body heating was then performed to engage cutaneous active vasodilation and was maintained until CVC had plateaued at an elevated level at all sites for 5-10 min. Finally, 58 mM sodium nitroprusside was perfused through both microdialysis sites to effect maximal vasodilation. No CVC differences were found between control and PACAP6-38-treated sites during normothermia (19 +/- 3%max untreated vs. 20 +/- 3%max, PACAP6-38 treated; P > 0.05 between sites) or cold stress (11 +/- 2%max untreated vs. 10 +/- 2%max, PACAP6-38 treated, P > 0.05 between sites). PACAP6-38 attenuated the increase in CVC during whole body heating when compared with untreated sites (59 +/- 3%max untreated vs. 46 +/- 3%max, PACAP6-38 treated, P < 0.05). We conclude that VPAC2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA. kelloggd@uthscsa.edu
authors.forename: Dean L
authors.initials: DL
authors.lastname: Kellogg
authors.forename: Joan L
authors.initials: JL
authors.lastname: Zhao
authors.forename: Yubo
authors.initials: Y
authors.lastname: Wu
authors.forename: John M
authors.initials: JM
authors.lastname: Johnson
mesh_terms: D000328:Adult; D001833:Body Temperature Regulation / Q000502:physiology; D005260:Female; D005542:Forearm; D018869:Heat-Shock Response / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology / Q000502:physiology; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000037:antagonists & inhibitors / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000037:antagonists & inhibitors / Q000502:physiology*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014665:Vasodilator Agents; D009599:Nitroprusside; D014660:Vasoactive Intestinal Peptide
references.citation: Am J Physiol Heart Circ Physiol. 2004 Sep;287(3):H1404-9
references.pmid: 15165988
references.citation: Recept Channels. 2002;8(3-4):137-53
references.pmid: 12529932
references.citation: Arch Dermatol Res. 1999 Apr;291(4):201-6
references.pmid: 10335916
references.citation: J Appl Physiol (1985). 2000 Feb;88(2):467-72
references.pmid: 10658012
references.citation: J Appl Physiol (1985). 2004 Oct;97(4):1291-8
references.pmid: 15155712
references.citation: Inflamm Res. 1998 Dec;47(12):488-92
references.pmid: 9892043
references.citation: J Appl Physiol (1985). 2005 Dec;99(6):2294-301
references.pmid: 16109832
references.citation: J Physiol. 2006 Dec 15;577(Pt 3):1043-51
references.pmid: 17023511
references.citation: Med Biol. 1986;64(2-3):67-73
references.pmid: 2427899
references.citation: J Appl Physiol (1985). 2006 May;100(5):1709-18
references.pmid: 16614368
references.citation: J Appl Physiol (1985). 2002 Dec;93(6):1947-51
references.pmid: 12391110
references.citation: J Invest Dermatol. 1994 May;102(5):807-11
references.pmid: 8176267
references.citation: J Appl Physiol (1985). 1990 Dec;69(6):2149-54
references.pmid: 1706332
references.citation: Neuropharmacology. 2006 Nov;51(6):1086-98
references.pmid: 16930633
references.citation: Br J Dermatol. 1990 Jul;123(1):65-76
references.pmid: 2390496
references.citation: Physiol Rev. 2006 Oct;86(4):1309-79
references.pmid: 17015491
references.citation: Pharmacol Rev. 2004 Jun;56(2):249-90
references.pmid: 15169929
references.citation: Endocrinology. 1994 Dec;135(6):2662-80
references.pmid: 7988457
references.citation: Circ Res. 1995 Dec;77(6):1222-8
references.pmid: 7586235
references.citation: J Cutan Pathol. 2002 Feb;29(2):65-71
references.pmid: 12150135
references.citation: J Invest Dermatol. 2001 Sep;117(3):754-6
references.pmid: 11564190
references.citation: J Physiol. 2005 Nov 1;568(Pt 3):1047-56
references.pmid: 16123103
references.citation: J Appl Physiol (1985). 2009 Apr;106(4):1112-8
references.pmid: 19196910
references.citation: Peptides. 2007 Sep;28(9):1631-9
references.pmid: 17574305
references.citation: J Physiol. 1980 Sep;306:537-52
references.pmid: 7463376
references.citation: J Physiol. 1957 May 23;136(3):489-97
references.pmid: 13429515
references.citation: J Appl Physiol (1985). 2007 Sep;103(3):963-8
references.pmid: 17600158
references.citation: Nature. 1980 Apr 10;284(5756):515-21
references.pmid: 6154244
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1981 Apr;50(4):814-8
references.pmid: 7263365
references.citation: Ann N Y Acad Sci. 2006 Jul;1070:239-42
references.pmid: 16888173
references.citation: J Pharmacol Exp Ther. 2003 Aug;306(2):638-45
references.pmid: 12750439
references.citation: Ann Neurol. 2006 Feb;59(2):376-81
references.pmid: 16437571
references.citation: Endocrinology. 2002 Apr;143(4):1327-36
references.pmid: 11897689
references.citation: J Appl Physiol (1985). 2007 Jun;102(6):2301-6
references.pmid: 17412796
references.citation: Br J Dermatol. 1987 Mar;116(3):323-8
references.pmid: 3567070
references.citation: Peptides. 1997;18(10):1555-60
references.pmid: 9437716
references.citation: J Cardiovasc Pharmacol. 1992 Jul;20(1):83-7
references.pmid: 1383635
references.citation: Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1601-9
references.pmid: 16306217
references.citation: Regul Pept. 1999 Mar 17;80(1-2):49-55
references.pmid: 10235634
references.citation: J Physiol. 2003 Oct 1;552(Pt 1):223-32
references.pmid: 12847205
references.citation: J Appl Physiol (1985). 1989 Apr;66(4):1586-92
references.pmid: 2732150
references.citation: Regul Pept. 2002 Oct 15;108(2-3):165-73
references.pmid: 12220741
references.citation: J Investig Dermatol Symp Proc. 1997 Aug;2(1):49-55
references.pmid: 9487016
references.citation: J Appl Physiol (1985). 1988 Jul;65(1):478-81
references.pmid: 3042745
references.citation: Circ Res. 1969 May;24(5):711-24
references.pmid: 5770258
references.citation: Peptides. 2004 Mar;25(3):393-401
references.pmid: 15134862
references.citation: Pharmacol Rev. 1998 Jun;50(2):265-70
references.pmid: 9647867
references.citation: J Allergy Clin Immunol. 2003 May;111(5):1099-105
references.pmid: 12743576
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Sep;297(3):R546-55
references.pmid: 19571208
references.citation: Eur J Histochem. 2002;46(3):223-8
references.pmid: 12472117
references.citation: J Appl Physiol (1985). 2005 Mar;98(3):829-37
references.pmid: 15489258