VPAC1 And / Or PAC1 Receptors Participate in Cutaneous Active Vasodilation during Heat Stress in Humans

Abstract

Vasoactive Intestinal Peptide (VIP) has been implicated in cutaneous active vasodilation (AVD) during heat stress in humans. Effects of VIP and related neuropeptides are mediated by several receptor types. We examined participation of VPAC1 and/or PAC1 receptors in cutaneous vasodilation during heat stress by testing the effects of specific blockade of these receptors on AVD. The VPAC1/PAC1 antagonist, Pituitary Adenylate Cyclase Activating Peptide 6–38 (PACAP 6–38) was administered by intradermal microdialysis. One site was treated with PACAP 6–38 through MD. The second site was perfused with Ringer's solution only. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry (LDF) at those sites. Body temperature was controlled with water-perfused suits. Blood pressure was monitored by Finapres and cutaneous vascular conductance calculated (CVC=LDF/MAP). The protocol began with 5 minute baseline period without PACAP 6–38 perfusion. This was followed by approximately 70 minutes of PACAP 6–38 perfusion at one site in normothermia. Normothermia was followed by a 3 minute period of whole body cooling (CS). Whole body heating was then performed to effect heat stress (HS) and activate AVD. After HS, 58mM sodium nitroprusside was perfused through both MD sites to effect maximal vasodilation for data normalization. No differences were found between Ringer's and PACAP 6–38 treated sites during normothermia (p>0.05 between sites) or cold stress (p>0.05 between sites). PACAP 6–38 attenuated the extent of AVD in HS when compared to untreated sites (p=0.05, n=6). We conclude that VPAC1 and/or PAC1 receptors play an important role in AVD in HS in humans. (supported by NIH Grant HL065599)