title: Histamine paw edema of mice was increased and became H2-antagonist sensitive by co-injection of nitric oxide forming agents, but serotonin paw edema was decreased.
abstract: Nitric oxide (NO) surprisingly caused the opposite effect on histamine and serotonin edema. The local injection of acidified nitrite (0.3-30 micrograms/paw which correspond 10 micrograms-1 mg/kg) increased histamine edema of mice up to 45 +/- 4% and suppressed serotonin edema to 90 +/- 3%. Other NO-generators (nitroprusside sodium and hydroxylamine) showed similar effects. These results were in accordance with our previous data on endogenous NO. Methylene blue (MB, 30 ng/paw which corresponds to 1 microgram/kg) suppressed histamine edema (62 +/- 3%) and increased serotonin edema (43 +/- 3%) in normal mice, being reversed by acidified nitrite. This suggests the involvement of guanosine 3',5'-cyclic monophosphate (cGMP) formation for the action of NO. Histamine edema became sensitive to H2-antagonist, cimetidine, by co-injection of 30 micrograms/paw (which corresponds to 1 mg/kg) acidified nitrite (ED50 = 30 micrograms/kg versus >> 1 mg/kg). NO seemed to modify the histamine receptor(s) or tautomeric form of histamine. NO, O2- and other oxyradicals might finely control the vascular permeability together with inflammatory mediators.
authors.affiliation: Drug Development Laboratories, Fujisawa Pharmaceutical Co, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oyanagui
authors.forename: S
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D004487:Edema / Q000503:physiopathology*; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*
chemical_list: D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D009573:Nitrites; D009569:Nitric Oxide; D012701:Serotonin; D006632:Histamine