Vasoactive intestinal peptide fragment VIP10-28 and active vasodilation in human skin

A recent study reported the vasoactive intestinal peptide ( VIP) fragment VIP10 - 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 VIP10 - 28 to antagonize VIP- mediated dilation in the presence of NO synthase ( NOS) inhibition and an H1 antagonist. Study 1 ( n = 12) examined whether VIP10 - 28 antagonizes vasodilation to exogenous VIP via inhibition of NO- dependent mechanisms. Study 2 ( n = 6) investigated AVD in skin sites receiving VIP10 - 28 alone and in combination with NOS inhibition. Study 3 ( n = 6) examined AVD in sites receiving VIP10 - 28 alone and combined VIP10 - 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). VIP10 - 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. VIP10 - 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 VIP10 - 28 may be an unsuitable antagonist for examining a role for VIP- mediated dilation in human skin.