title: Evidence for a role for vasoactive intestinal peptide in active vasodilatation in the cutaneous vasculature of humans.
abstract: Active vasodilatation (AVD) in human, non-glabrous skin depends on functional cholinergic fibres but not on acetylcholine (ACh). We tested whether AVD is a redundant system in which ACh and vasoactive intestinal polypeptide (VIP) are co-released from cholinergic nerves. (1) We administered VIP by intradermal microdialysis to four discrete areas of skin in the presence of different levels of the VIP receptor antagonist, VIP(10-28), also delivered by microdialysis. Skin blood flow (SkBF) was continuously monitored by laser Doppler flowmetry (LDF). Mean arterial pressure (MAP) was measured non-invasively and cutaneous vascular conductance (CVC) calculated as LDF/MAP. Subjects were supine and wore water-perfused suits to control whole-body skin temperature (Tsk) at 34 degrees C. Concentrations of 54 microM, 107 microM, or 214 microM VIP(10-28) were perfused via intradermal microdialysis at 2 microl min-1 for approximately 1 h. Then 7.5 microM VIP was added to the perfusate containing VIP(10-28) at the three concentrations or Ringer solution and perfusion was continued for 45-60 min. At the control site, this level of VIP caused approximately the vasodilatation typical of heat stress. All VIP(10-28)-treated sites displayed an attenuated dilatation in response to the VIP. The greatest attenuation was observed at the site that received 214 microM VIP(10-28) (P < 0.01). (2) We used 214 microM VIP(10-28) alone and with the iontophoretically administered muscarinic receptor antagonist atropine (400 microA cm-2, 45 s, 10 mM) in heated subjects to test the roles of VIP and ACh in AVD. Ringer solution and 214 microM VIP(10-28) were each perfused at two sites, one of which in each case was pretreated with atropine. After 1 h of VIP(10-28) treatment, individuals underwent 45-60 min of whole-body heating (Tsk to 38.5 degrees C). VIP(10-28), alone or in combination with atropine, attenuated the increase in CVC during heat stress, suggesting an important role for VIP in AVD.
authors.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Lee Ann T
authors.initials: LA
authors.lastname: Bennett
authors.forename: John M
authors.initials: JM
authors.lastname: Johnson
authors.forename: Dan P
authors.initials: DP
authors.lastname: Stephens
authors.forename: Adham R
authors.initials: AR
authors.lastname: Saad
authors.forename: Dean L
authors.initials: DL
authors.lastname: Kellogg
mesh_terms: D000328:Adult; D001285:Atropine / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000502:physiology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D005260:Female; D018882:Heat Stress Disorders / Q000503:physiopathology*; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D017551:Microdialysis; D010276:Parasympatholytics / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000294:innervation; D012881:Skin Temperature / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D010276:Parasympatholytics; D010446:Peptide Fragments; D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28); D001285:Atropine