Active vasodilatation (AVD) in human, non-glabrous skin depends on functional cholinergic fibres but not on acetylcholine (ACh). We tested whether AVD is a redundant system in which ACh and vasoactive intestinal polypeptide (VIP) are co-released from cholinergic nerves. (1) We administered VIP by intradermal microdialysis to four discrete areas of skin in the presence of different levels of the VIP receptor antagonist, VIP(10-28), also delivered by microdialysis. Skin blood flow (SkBF) was continuously monitored by laser Doppler flowmetry (LDF). Mean arterial pressure (MAP) was measured non-invasively and cutaneous vascular conductance (CVC) calculated as LDF/MAP. Subjects were supine and wore water-perfused suits to control whole-body skin temperature (Tsk) at 34°C. Concentrations of 54 μM, 107 μM, or 214 μM VIP(10-28) were perfused via intradermal microdialysis at 2 μl min-1 for approximately 1 h. Then 7.5 μM VIP was added to the perfusate containing VIP(10-28) at the three concentrations or Ringer solution and perfusion was continued for 45-60 min. At the control site, this level of VIP caused approximately the vasodilatation typical of heat stress. All VIP(10-28)-treated sites displayed an attenuated dilatation in response to the VIP. The greatest attenuation was observed at the site that received 214 μM VIP(10-28) (P < 0.01 . (2) We used 214 μM VIP(10-28) alone and with the iontophoretically administered muscarinic receptor antagonist atropine (400 μA cm-2 , 45 s, 10 mM) in heated subjects to test the roles of VIP and ACh in AVD. Ringer solution and 214 μM VIP(10-28) were each perfused at two sites, one of which in each case was pretreated with atropine. After 1 h of VIP(10-28) treatment, individuals underwent 45-60 min of whole-body heating (Tsk to 38.5°C). VIP(10-28), alone or in combination with atropine, attenuated the increase in CVC during heat stress, suggesting an important role for VIP in AVD.
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