Evidence for a Role for Vasoactive Intestinal Peptide in Active Vasodilatation in the Cutaneous Vasculature of Humans

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Abstract
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.