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1Department of Human Physiology, and 2Institute of Neuroscience, University of Oregon, Eugene, Oregon
Submitted 2 May 2005 ; accepted in final form 9 August 2005
A recent study reported the vasoactive intestinal peptide (VIP) fragment VIP1028 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 VIP1028 to antagonize VIP-mediated dilation in the presence of NO synthase (NOS) inhibition and an H1 antagonist. Study 1 (n = 12) examined whether VIP1028 antagonizes vasodilation to exogenous VIP via inhibition of NO-dependent mechanisms. Study 2 (n = 6) investigated AVD in skin sites receiving VIP1028 alone and in combination with NOS inhibition. Study 3 (n = 6) examined AVD in sites receiving VIP1028 alone and combined VIP1028 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). VIP1028 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. VIP1028). 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 VIP1028 may be an unsuitable antagonist for examining a role for VIP-mediated dilation in human skin.
histamine receptor-1; cutaneous vascular conductance
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