Acetylcholine-induced vasodilation is mediated by nitric oxide and prostaglandins in human skin

J Appl Physiol (1985). 2005 Feb;98(2):629-32. doi: 10.1152/japplphysiol.00728.2004.


Acetylcholine (ACh) can effect vasodilation by several mechanisms, including activation of endothelial nitric oxide (NO) synthase and prostaglandin (PG) production. In human skin, exogenous ACh increases both skin blood flow (SkBF) and bioavailable NO levels, but the relative increase is much greater in SkBF than NO. This led us to speculate ACh may dilate cutaneous blood vessels through PGs, as well as NO. To test this hypothesis, we performed a study in 11 healthy people. We measured SkBF by laser-Doppler flowmetry (LDF) at four skin sites instrumented for intradermal microdialysis. One site was treated with ketorolac (Keto), a nonselective cyclooxygenase antagonist. A second site was treated with NG-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase. A third site was treated with a combination of Keto and L-NAME. The fourth site was an untreated control site. After the three treated sites received the different inhibiting agents, ACh was administered to all four sites by intradermal microdialysis. Finally, sodium nitroprusside (SNP) was administered to all four sites. Mean arterial pressure (MAP) was monitored by Finapres, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). For data analysis, CVC values for each site were normalized to their respective maxima as effected by SNP. The results showed that both Keto and L-NAME each attenuated the vasodilation induced by exogenous ACh (ACh control = 79 +/- 4% maximal CVC, Keto = 55 +/- 7% maximal CVC, L-NAME = 46 +/- 6% maximal CVC; P < 0.05, ACh vs. Keto or L-NAME). The combination of the two agents produced an even greater attenuation of ACh-induced vasodilation (31 +/- 5% maximal CVC; P < 0.05 vs. all other sites). We conclude that a portion of the vasodilation effected by exogenous ACh in skin is due to NO; however, a significant portion is also mediated by PGs.

Publication types

  • Clinical Trial

MeSH terms

  • Acetylcholine / pharmacology*
  • Adult
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Female
  • Humans
  • Male
  • Nitric Oxide / metabolism*
  • Prostaglandins / metabolism*
  • Skin / blood supply*
  • Skin / drug effects
  • Skin Physiological Phenomena / drug effects*
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology*


  • Prostaglandins
  • Nitric Oxide
  • Acetylcholine