VPAC2 And/Or PAC1 Receptors Interact with NOS during Heat Stress in Humans

Abstract

VPAC2 and/or PAC1 receptors are implicated in cutaneous active vasodilation(AVD) during heat stress(HS). Nitric oxide(NO) from NOS also plays important roles in HS in humans. We hypothesized that NO and VPAC2/PAC1 interact in AVD during HS. We examined this interaction by testing the effects of specific blockade of these receptors with and without NOS inhibition during HS. The VPAC2/PAC1 antagonist, Pituitary Adenylate Cyclase Activating Peptide 6‐38(PACAP6‐38) and the NOS inhibitor, L‐NAME(LNM) were used. PACAP6‐38, LNM, a combination(MIX) of PACAP6‐38 and LNM, or Ringer's solution alone were perfused at 4 separate intradermal microdialysis sites. Skin blood flow(SkBF) was monitored by aser‐Doppler flowmetry and body temperature controlled with water‐perfused suits. The protocol began with a 10 minute baseline period without antagonist perfusion. This was followed by 45 minutes of PACAP6‐38, L‐NM or Mix perfusion at respective site in normothermia(Norm). Norm was followed by a 3‐minute period of whole body cooling (CS). Whole body heating was then performed to effect HS and activate AVD. After HS, 58mM sodium nitroprusside was perfused at all MD sites to effect maximal vasodilation for data normalization. No differences were found between Ringer's and PACAP6‐38, L‐NAME, or MIX sites during Norm(p>0.05 among sites) or CS(p>0.05 among sites). All three treated sites attenuated AVD in HS when compared to Ringer's sites(p<0.05). Greater attenuation occurred at LNM and MIX sites than in PACAP6‐38 sites(p<0.05); however, AVD attenuation was not different between LNM and MIX treated sites(P>0.05, LNM vs MIX). We conclude that VPAC2/PAC1 receptors interact with NO during AVD. (supported by NIH Grant HL065599)