NO-mediated activation of K ATP channels contributes to cutaneous thermal hyperemia in young adults

Am J Physiol Regul Integr Comp Physiol. 2020 Feb 1;318(2):R390-R398. doi: 10.1152/ajpregu.00176.2019. Epub 2020 Jan 8.

Abstract

Local skin heating to 42°C causes cutaneous thermal hyperemia 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 hyperemia. In 13 young adults (6 women, 7 men), cutaneous vascular conductance (CVC) was measured at four intradermal microdialysis sites that were continuously perfused with 1) lactated Ringer solution (control), 2) 5 mM glibenclamide (KATP channel blocker), 3) 20 mM NG-nitro-l-arginine methyl ester (NOS inhibitor), or 4) a combination of KATP channel blocker and NOS inhibitor. Local skin heating to 42°C was administered at all four treatment sites to elicit cutaneous thermal hyperemia. Thirty minutes after the local heating, 1.25 mM pinacidil (KATP channel opener) and subsequently 25 mM sodium nitroprusside (NO donor) were administered to three of the four 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 hyperemia. This interplay may reflect a vascular smooth muscle cell KATP channel activation by NO.

Keywords: NOS; depolarization; hyperpolarization; microcirculation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Flow Velocity
  • Enzyme Inhibitors / administration & dosage
  • Female
  • Humans
  • Hyperemia / enzymology*
  • Hyperemia / etiology
  • Hyperemia / physiopathology
  • Hypothermia, Induced
  • Ion Channel Gating
  • KATP Channels / antagonists & inhibitors
  • KATP Channels / metabolism*
  • Male
  • Microcirculation* / drug effects
  • Microvessels / drug effects
  • Microvessels / enzymology*
  • Microvessels / physiopathology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / administration & dosage
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Potassium Channel Blockers / administration & dosage
  • Signal Transduction
  • Skin / blood supply*
  • Vasodilation* / drug effects
  • Vasodilator Agents / administration & dosage
  • Young Adult

Substances

  • Enzyme Inhibitors
  • KATP Channels
  • Nitric Oxide Donors
  • Potassium Channel Blockers
  • Vasodilator Agents
  • Nitric Oxide
  • Nitric Oxide Synthase