Separate and combined effects of K Ca and K ATP channel blockade with NOS inhibition on cutaneous vasodilation and sweating in older men during heat stress

Am J Physiol Regul Integr Comp Physiol. 2019 Jul 1;317(1):R113-R120. doi: 10.1152/ajpregu.00075.2019. Epub 2019 May 15.

Abstract

Our objective in this study was to examine the separate and combined effects of potassium (K+) channels and nitric oxide synthase (NOS) on cutaneous vasodilation and sweating in older men during rest and exercise in the heat. In 13 habitually active men (61 ± 4 yr), cutaneous vascular conductance and local sweat rate were assessed at six dorsal forearm skin sites continuously perfused with either 1) lactated Ringer (control), 2) 10 mM NG-nitro-l-arginine methyl ester (l-NAME, NOS inhibitor), 3) 50 mM tetraethylammonium (TEA; Ca2+-activated K+ channel blocker), 4) 5 mM glybenclamide (GLY; ATP-sensitive K+ channel blocker), 5) 50 mM TEA + 10 mM l-NAME, and 6) 5 mM GLY + 10 mM l-NAME via microdialysis. Participants rested in non-heat stress (25°C) and heat stress (35°C) conditions for ∼60 min each, followed by 50 min of moderate-intensity cycling (∼55% V̇o2peak) and 30 min of recovery in the heat. During rest and exercise in the heat, l-NAME, TEA + l-NAME, and GLY + l-NAME attenuated CVC relative to control (all P ≤ 0.05), although l-NAME was not different from TEA + l-NAME or GLY + l-NAME (all P > 0.05). TEA attenuated CVC during rest, whereas GLY attenuated CVC during exercise (both P ≤ 0.05). Additionally, whereas neither l-NAME nor TEA altered sweating throughout the protocol (all P > 0.05), combined TEA + l-NAME attenuated sweating during exercise in the heat (P ≤ 0.05). We conclude that in habitually active older men blockade of KCa and KATP channels attenuates cutaneous vasodilation during rest and exercise in the heat, respectively, and these effects are NOS dependent. Furthermore, combined NOS inhibition and KCa channel blockade attenuates sweating during exercise in the heat.

Keywords: aging; heat loss; hyperpolarization; microcirculation; potassium channel; skin blood flow; thermoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Enzyme Inhibitors / pharmacology
  • Glyburide / administration & dosage
  • Glyburide / pharmacology
  • Heat-Shock Response / physiology*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • KATP Channels / antagonists & inhibitors*
  • KATP Channels / metabolism
  • Male
  • Middle Aged
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors*
  • Potassium Channels, Calcium-Activated / metabolism
  • Sweating / drug effects
  • Tetraethylammonium / administration & dosage
  • Tetraethylammonium / pharmacology
  • Vasodilation / drug effects*

Substances

  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • KATP Channels
  • Potassium Channel Blockers
  • Potassium Channels, Calcium-Activated
  • Tetraethylammonium
  • Nitric Oxide Synthase
  • Glyburide
  • NG-Nitroarginine Methyl Ester