Sex-differences in cholinergic, nicotinic, and β-adrenergic cutaneous vasodilation: Roles of nitric oxide synthase, cyclooxygenase, and K+ channels

Microvasc Res. 2020 Sep:131:104030. doi: 10.1016/j.mvr.2020.104030. Epub 2020 Jun 9.


Previous studies indicate that sex-related differences exist in the regulation of cutaneous vasodilation, however, the mechanisms remain unresolved. We assessed if sex-differences in young adults exist for cholinergic, nicotinic, and β-adrenergic cutaneous vasodilation with a focus on nitric oxide synthase (NOS), cyclooxygenase (COX), and K+ channel mechanisms. In twelve young men and thirteen young women, four intradermal forearm skin sites were perfused with the following: 1) lactated Ringer's solution (control), 2) 10 mM Nω-nitro-l-arginine, a non-selective NOS inhibitor, 3) 10 mM ketorolac, a non-selective COX inhibitor, or 4) 50 mM BaCl2, a nonspecific K+ channel blocker. At all four sites, cutaneous vasodilation was induced by 1) 10 mM nicotine, a nicotinic receptor agonist, 2) 100 μM isoproterenol, a nonselective β-adrenergic receptor agonist, and 3) 2 mM and 2000 mM acetylcholine, an acetylcholine receptor agonist. Nicotine and isoproterenol were administered for 3 min, whereas each acetylcholine dose was administered for 25 min. Regardless of treatment site, cutaneous vasodilation in response to nicotine and a high dose of acetylcholine (2000 mM) were lower in women than men. By contrast, isoproterenol induced cutaneous vasodilation was greater in women vs. men. Irrespective of sex, NOS inhibition or K+ channel blockade attenuated isoproterenol-mediated cutaneous vasodilation, whereas K+ channel blockade decreased nicotine-induced cutaneous vasodilation. Taken together, our findings indicate that while the mechanisms underlying cutaneous vasodilation are comparable between young men and women, sex-related differences in the magnitude of cutaneous vasodilation do exist and this response differs as a function of the receptor agonist.

Keywords: AChR microcirculation; Acetylcholine; Adrenaline; Endothelium-dependent vasodilation; Thermoregulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adult
  • Blood Vessels / drug effects
  • Blood Vessels / enzymology*
  • Cholinergic Agonists / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Female
  • Forearm
  • Humans
  • Male
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Receptors, Adrenergic, beta / metabolism*
  • Receptors, Cholinergic / metabolism*
  • Receptors, Nicotinic / metabolism
  • Sex Factors
  • Signal Transduction
  • Skin / blood supply*
  • Vasodilation* / drug effects
  • Young Adult


  • Adrenergic beta-Agonists
  • Cholinergic Agonists
  • Cyclooxygenase Inhibitors
  • Potassium Channel Blockers
  • Potassium Channels
  • Receptors, Adrenergic, beta
  • Receptors, Cholinergic
  • Receptors, Nicotinic
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Prostaglandin-Endoperoxide Synthases