Contribution of neurokinin‐1 receptor activation to cutaneous active vasodilation in humans

The precise mechanisms underlying active vasodilation remain unclear. The purpose of this study was to determine the contribution of neurokinin‐1 (NK 1 ) receptors to active vasodilation. We exploited our previous findings that consecutive microdialysis infusions of substance P (SP) desensitize NK 1 receptors. Eleven subjects were equipped with four microdialysis fibers. Site 1 served as control and was perfused with Ringer's solution. Site 2 was perfused with 10mM L‐NAME to inhibit NO synthase. Site 3 received a 10μM dose of SP to desensitize NK 1 receptors prior to whole body heating. Site 4 received 10μM SP combined with 10mM L‐NAME. Laser‐Doppler flowmetry was used as an index of skin blood flow and cutaneous vascular conductance (CVC) was calculated and normalized to maximal. SP was infused in sites 3 and 4 for 15 min at a rate of 4μl min −1 and skin blood flow was allowed to return to baseline. Subjects underwent whole body heating to raise oral temperature 0.8°C above baseline. During whole body heating, CVC in control sites increased to 69 ± 3 %CVC max . SP‐treated sites (48 ± 3 %CVC max ) were significantly reduced compared to control sites. In L‐NAME sites, CVC was significantly reduced (32 ± 3 %CVC max ) compared to both control and SP‐treated sites. The CVC response to whole body heating was nearly abolished in SP‐treated sites combined with L‐NAME (20 ± 2 %CVC max ). These data suggest NK 1 receptors directly contribute to a portion of active vasodilation and work independently of NO. Support: NIH HL‐70928 and Eugene Evonuk Fellowship