Voltage-gated potassium channels and NOS contribute to a sustained cutaneous vasodilation elicited by local heating in an interactive manner in young adults

Microvasc Res. 2018 May;117:22-27. doi: 10.1016/j.mvr.2017.12.001. Epub 2017 Dec 13.

Abstract

Local skin heating to 42°C causes rapid increases in cutaneous perfusion (initial peak), followed by a brief nadir and subsequent sustained elevation (plateau). Several studies have demonstrated that nitric oxide synthase (NOS) largely contributes to the plateau response during local heating. In this study, we tested the hypothesis that voltage-gated potassium (Kv) channels contribute to the plateau of the cutaneous vasodilation during local heating through NOS-dependent mechanisms. Eleven young males (25±4years) participated in this study wherein cutaneous vascular conductance (CVC) was measured at four intradermal microdialysis sites that were continuously perfused with either 1) lactated Ringer (Control), 2) 10mM 4-aminopyridine (Kv channel blocker), 3) 10mM Nω-Nitro-L-arginine (NOS inhibitor), or 4) a combination of 4-aminopyridine and Nω-Nitro-L-arginine. In comparison to the Control site, the inhibition of Kv channels alone attenuated the increase in CVC observed at the initial peak, nadir, and plateau phases measured during local heating; in contrast, the inhibition of NOS alone attenuated the increase in CVC at the nadir and plateau phases only (e.g., plateau response: Control site: 59±5%max, Kv channel blockade site: 49±8%max, NOS inhibition site: 35±11%max, combined inhibition site: 40±12%max). Further, no effect of Kv channel blockade on CVC was measured at any phase of the local heating response when the modulating influence of NOS was simultaneously removed. We show that Kv channels and NOS contribute to the local heating mediated sustained increase (i.e., plateau) in cutaneous vasodilation in an interactive manner. (243/250 words).

Keywords: Depolarization; Hyperpolarization; Microcirculation; NOS; Thermal hyperemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Arteries / drug effects
  • Arteries / enzymology*
  • Enzyme Inhibitors / administration & dosage
  • Heating*
  • Humans
  • Hyperthermia, Induced*
  • Male
  • Microdialysis
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Potassium Channel Blockers / administration & dosage
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors
  • Potassium Channels, Voltage-Gated / metabolism*
  • Signal Transduction
  • Skin / blood supply*
  • Vasodilation* / drug effects
  • Young Adult

Substances

  • Enzyme Inhibitors
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Nitric Oxide
  • Nitric Oxide Synthase