Local skin heating to 42ºC causes cutaneous thermal hyperaemia largely via nitric oxide (NO) synthase (NOS) related mechanisms. We assessed the hypothesis that ATP-sensitive K+ (KATP) channels interact with NOS to mediate cutaneous thermal hyperaemia. In thirteen young adults (6 women), cutaneous vascular conductance (CVC) was measured at four intradermal microdialysis sites that were continuously perfused with either 1) lactated Ringer's solution (control), 2) 5 mM glibenclamide (KATP channel

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... locker), 3) 20mM N(G)-Nitro-L-arginine methyl ester (NOS inhibitor), or 4) a combination of both. Local skin heating to 42ºC was administered at all four treatment sites to elicit cutaneous thermal hyperaemia. Thirty minutes after the local heating, 1.25 mM pinacidil (KATP channel opener) and subsequently 25 mM sodium nitroprusside (NO donor) were administered to 3 of the 4 sites (each 25-30 min). The local-heating induced prolonged elevation in CVC was attenuated by glibenclamide (19%), but the transient initial peak was not. However, glibenclamide had no effect on the prolonged elevation in CVC in the presence of NOS inhibition. Pinacidil caused an elevation in CVC, but this response was abolished at the glibenclamide treated skin site, demonstrating its effectiveness as a KATP channel blocker. The pinacidil-induced increase in CVC was unaffected by NOS inhibition, whereas the increase in CVC elicited by sodium nitroprusside was partly (15%) inhibited by glibenclamide. In summary, we showed an interactive effect of KATP channels and NOS for the plateau of cutaneous thermal hyperaemia. This interplay may reflect a vascular smooth muscle cell KATP channel activation by NO.