Vasoactive intestinal peptide fragment VIP10-28 and active vasodilation in human skin.
A recent study reported the vasoactive intestinal peptide (VIP) fragment VIP(10-28) inhibited the rise in skin blood flow during heat stress. Our laboratory has reported that the nitric oxide (NO) pathway and histamine receptor-1 (H1)-receptor activation is common to both exogenous VIP-mediated dilation and active vasodilation (AVD). The present study aimed to further examine the specific role for VIP in AVD by using VIP(10-28) to antagonize VIP-mediated dilation in the presence of NO synthase (NOS) inhibition and an H1 antagonist. Study 1 (n = 12) examined whether VIP(10-28) antagonizes vasodilation to exogenous VIP via inhibition of NO-dependent mechanisms. Study 2 (n = 6) investigated AVD in skin sites receiving VIP(10-28) alone and in combination with NOS inhibition. Study 3 (n = 6) examined AVD in sites receiving VIP(10-28) alone and combined VIP(10-28) and H1 antagonism. Due to differences in our findings and those previously published, study 4 (n = 6) investigated whether an increase in baseline skin blood flow could result in a diminished rise in AVD. Red blood cell flux was measured using laser Doppler flowmetry, and cutaneous vascular conductance (flux/mean arterial pressure) was normalized to maximal vasodilation (28 mM sodium nitroprusside). VIP(10-28) augmented vasodilation to exogenous VIP (P < 0.05 vs. control) and hyperthermia (P < 0.05 vs. control). NOS inhibition had no effect on the augmented dilation during exogenous VIP or hyperthermia (P > 0.05). Similarly, H1-receptor antagonists had no effect on the augmented dilation during hyperthermia (P > 0.05 vs. VIP(10-28)). In study 4, percentage of maximal cutaneous vascular conductance was attenuated when baseline skin blood flow was elevated before whole body heating. Our results suggest that VIP(10-28) may be an unsuitable antagonist for examining a role for VIP-mediated dilation in human skin.
Wilkins
Brad W
BW
Dept. of Human Physiology, University of Oregon, Eugene, OR 97403-1240, USA.
Wong
Brett J
BJ
Tublitz
Nathan J
NJ
McCord
Gregg R
GR
Minson
Christopher T
CT
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D010446:Peptide Fragments / Q000008:administration & dosage*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D010446:Peptide Fragments; D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28)