KCa channels are major contributors to ATP-induced cutaneous vasodilation in healthy older adults

Microvasc Res. 2021 Jan:133:104096. doi: 10.1016/j.mvr.2020.104096. Epub 2020 Oct 13.

Abstract

Objective: To examine the contributions of calcium-activated K+ (KCa) channels and nitric oxide synthase (NOS) to adenosine triphosphate (ATP)-induced cutaneous vasodilation in healthy older adults.

Methods: In eleven older adults (69 ± 2 years, 5 females), cutaneous vascular conductance, normalized to maximum vasodilation (%CVCmax) was assessed at four dorsal forearm skin sites that were continuously perfused with either 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (TEA, KCa channel blocker), 3) 10 mM Nω-nitro-L-arginine (L-NNA, NOS inhibitor), or 4) combined 50 mM TEA +10 mM L-NNA, via microdialysis. Local skin temperature was fixed at 33 °C at all sites with local heaters throughout the protocol while the cutaneous vasodilator response was assessed during coadministration of ATP (0.03, 0.3, 3, 30, 300 mM; 20 min per dose), followed by 50 mM sodium nitroprusside and local skin heating to 43 °C to achieve maximum vasodilation (20-30 min).

Results: Blockade of KCa channels blunted %CVCmax relative to Control from 0.3 to 300 mM ATP (All P < 0.05). A similar response was observed for the combined KCa channel blockade and NOS inhibition site from 3 to 300 mM ATP (All P < 0.05). Conversely, NOS inhibition alone did not influence %CVCmax across all ATP doses (All P > 0.05).

Conclusion: In healthy older adults, KCa channels play an important role in modulating ATP-induced cutaneous vasodilation, while the NOS contribution to this response is negligible.

Keywords: Heat loss; Microdialysis; Purinergic; Skin blood flow; Thermoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Age Factors
  • Aged
  • Blood Vessels / drug effects*
  • Blood Vessels / metabolism
  • Calcium Channel Blockers / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Male
  • Microdialysis
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors
  • Potassium Channels, Calcium-Activated / metabolism*
  • Signal Transduction
  • Skin / blood supply*
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology*

Substances

  • Calcium Channel Blockers
  • Enzyme Inhibitors
  • Potassium Channels, Calcium-Activated
  • Vasodilator Agents
  • Adenosine Triphosphate
  • Nitric Oxide Synthase