Possible role of nitric oxide in 5-hydroxytryptamine-induced increase in vascular permeability in mouse skin

Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):361-4. doi: 10.1007/BF00178952.


In order to test the hypothesis that a 5-hydroxytryptamine (5-HT)-induced increase in vascular permeability results from a cascade triggered by activation of the synthesis of nitric oxide (NO), the vascular permeability was investigated using the Pontamine sky blue leakage method in male mice. Subcutaneous injection of 5-HT induced a dose-related increase of vascular permeability at the injection site. The vascular permeability induced by 5-HT was inhibited by pretreatment with intraperitoneal injection of ketanserin (5-HT2A antagonist) and methysergide (5-HT1/2A antagonist), less efficiently by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine (NAN-190) (5-HT1A antagonist), but not by granisetron (5-HT3 antagonist). Increase in vascular permeability induced by 5-HT was inhibited by concurrent intravenous administration of NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue but not by the inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME). These results suggest that 5-HT increases vascular permeability by activating the 5-HT receptors and that endogenous NO is involved in this effect of 5-HT.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Capillary Permeability / drug effects*
  • Ketanserin
  • Male
  • Mice
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Skin / blood supply
  • Skin / drug effects*
  • Stereoisomerism


  • Serotonin Antagonists
  • Nitric Oxide
  • Serotonin
  • Arginine
  • Ketanserin
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • NG-Nitroarginine Methyl Ester