A Role for Histamine in Active Vasodilation

Abstract

0267 It has been established that nitric oxide (NO) is involved in cutaneous active vasodilation. Recent evidence suggests vasoactive intestinal peptide (VIP) may be involved in active vasodilation and we have recently shown that VIP-mediated dilation includes a substantial NO-dependent portion. Furthermore, VIP has been shown to induce histamine release from mast cells in human skin. Thus, it is possible that the NO portion of active vasodilation may be due to release of histamine. PURPOSE: To determine the relative contribution of NO and histamine during whole body heating. METHODS: Six subjects were instrumented with 4 microdialysis fibers. Site 1 served as a control and was infused with Ringer's solution. Site 2 received 10 mM L-NAME to inhibit NO synthase (NOS). Site 3 received the H1 receptor antagonist pyrilamine maleate (500 μM). Site 4 was infused with L-NAME combined with H1 receptor antagonist (final concentrations of 10 mM and 500 μM). All infusions were continuous beginning 30 minutes prior to whole body heating and throughout the duration of the heating period. Subjects wore a water-perfused suit and hot water was pumped through the suit to increase core temperature at least 0.8°C. Laser-Doppler flowmetery was used to monitor skin blood flow (SkBF) over each site. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure and normalized to maximal values via infusion of 28 mM sodium nitroprusside. RESULTS: In control sites, CVC increased during whole body heating to 69±3 %CVCmax. CVC values were significantly reduced in sites receiving NOS inhibition (32±2 %CVCmax; p<0.001) and in sites receiving H1 antagonist only (51±3 %CVCmax; p<0.05). CVC in sites that received NOS inhibition combined with H1 antagonist was attenuated compared to control (33±3 %CVCmax; p<0.001). However, there was no difference between NOS inhibited sites and combined NOS inhibitor and H1 antagonist sites. Additionally, NOS inhibited sites and combined NOS inhibitor and H1 antagonist sites were significantly reduced compared to H1 antagonist only sites (p<0.05). CONCLUSION: The increase in SkBF during whole body heating contains both a histamine component. Furthermore, these data are consistent with a role for VIP in active vasodilation. Supported by NIH Grant HL 70928