Evidence for a role for vasoactive intestinal peptide in active vasodilatation in the cutaneous vasculature of humans

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 (T-sk) at 34degreesC. Concentrations of 54 mum, 107 mum, or 214 mum VIP(10-28) were perfused via intradermal. microdialysis at 2 mul min(-1) for approximately I h. Then 7.5 mum 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 mum VIP(10-28) (P < 0.01). (2) We used 214 mum VIP(10-28) alone and with the iontophoretically administered muscarinic receptor antagonist atropine (400 muA cm(-2), 45s, 10 mm) in heated subjects to test the roles of VIP and ACh in AVD. Ringer solution and 214 mum VIP(10-28) were each perfused at two sites, one of which in each case was pretreated with atropine. After I h of VIP(10-28) treatment, individuals underwent 45-60 min of whole-body heating (T-sk to 38.5degreesC). 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.