Cutaneous blood flow during intradermal NO administration in young and older adults: roles for calcium-activated potassium channels and cyclooxygenase?

Am J Physiol Regul Integr Comp Physiol. 2016 Jun 1;310(11):R1081-7. doi: 10.1152/ajpregu.00041.2016. Epub 2016 Apr 6.

Abstract

Nitric oxide (NO) increases cutaneous blood flow; however, the underpinning mechanism(s) remains to be elucidated. We hypothesized that the cutaneous blood flow response during intradermal administration of sodium nitroprusside (SNP, a NO donor) is regulated by calcium-activated potassium (KCa) channels and cyclooxygenase (COX) in young adults. We also hypothesized that these contributions are diminished in older adults given that aging can downregulate KCa channels and reduce COX-derived vasodilator prostanoids. In 10 young (23 ± 5 yr) and 10 older (54 ± 4 yr) adults, cutaneous vascular conductance (CVC) was measured at four forearm skin sites infused with 1) Ringer (Control), 2) 50 mM tetraethylammonium (TEA), a nonspecific KCa channel blocker, 3) 10 mM ketorolac, a nonspecific COX inhibitor, or 4) 50 mM TEA + 10 mM ketorolac via intradermal microdialysis. All skin sites were coinfused with incremental doses of SNP (0.005, 0.05, 0.5, 5, and 50 mM each for 25 min). During SNP administration, CVC was similar at the ketorolac site (0.005-50 mM, all P > 0.05) relative to Control, but lower at the TEA and TEA + ketorolac sites (0.005-0.05 mM, all P < 0.05) in young adults. In older adults, ketorolac increased CVC relative to Control during 0.005-0.05 mM SNP administration (all P < 0.05), but this increase was not observed when TEA was coadministered (all P > 0.05). Furthermore, TEA alone did not modulate CVC during any concentration of SNP administration in older adults (all P > 0.05). We show that during low-dose NO administration (e.g., 0.005-0.05 mM), KCa channels contribute to cutaneous blood flow regulation in young adults; however, in older adults, COX inhibition increases cutaneous blood flow through a KCa channel-dependent mechanism.

Keywords: aging; endothelial cell; endothelium-derived hyperpolarizing factors; microcirculation; nitric oxide synthase; prostanoids; smooth muscle cell; soluble guanylyl cyclase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / drug effects
  • Aging / physiology*
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / administration & dosage*
  • Potassium Channels, Calcium-Activated / drug effects
  • Potassium Channels, Calcium-Activated / physiology*
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Skin Physiological Phenomena / drug effects*
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • Vasodilator Agents / administration & dosage

Substances

  • Potassium Channels, Calcium-Activated
  • Vasodilator Agents
  • Nitric Oxide
  • Prostaglandin-Endoperoxide Synthases