title: Pertussis toxin-induced histamine sensitisation: an aspecific phenomenon independent from the nitric oxide system?
abstract: Mechanisms were studied initially to develop an in vitro safety test for detecting pertussis toxin toxicity in acellular pertussis vaccines based on the histamine sensitisation test. Maximal contractions and sensitivities to different agonists and adrenoceptor-induced contractions in Ca2+-free medium of isolated rat small mesenteric resistance arteries were significantly reduced by in vivo [30 microg/kg, intravenously (i.v.), day 5] or in vitro (10 microg/ml, 2 h) pertussis toxin pretreatment. Pertussis toxin-induced decrease in sensitivity of small mesenteric resistance arteries to noradrenaline was endothelium-dependent. Nomega-nitro-L-arginine methyl ester (L-NAME) (100 microM, 20 min) did not reestablish the sensitivity to noradrenaline. In vivo L-NAME treatment (0, 1, 10 or 30 mg/kg) of pertussis toxin-pretreated (15 microg/kg) rats did not reduce pertussis toxin-induced enhancement of the histamine-induced decrease in blood pressure and histamine (10, 30, 100 or 300 mg/kg) induced mortality. Finally, in vivo pertussis toxin pretreatment sensitises rats for sodium nitroprusside (50 microg/kg/min). We conclude that pertussis toxin-induced histamine sensitisation is caused by an interference of pertussis toxin with the contractile mechanisms of vascular smooth muscle of resistance arteries which indicates only an indirect role for histamine in the histamine sensitisation test.
authors.affiliation: National Institute for Public Health and the Environment, Laboratory of Toxicology, Pathology and Genetics, P.O. Box 1, 3720 BA Bilthoven, The Netherlands. cokky.van.meijeren@rivm.nl
authors.forename: Cornelia E
authors.initials: CE
authors.lastname: van Meijeren
authors.forename: Wim
authors.initials: W
authors.lastname: Vleeming
authors.forename: Ton
authors.initials: T
authors.lastname: van de Kuil
authors.forename: Anne-Loes
authors.initials: AL
authors.lastname: Gerards
authors.forename: Coenraad F M
authors.initials: CF
authors.lastname: Hendriksen
authors.forename: Dick J
authors.initials: DJ
authors.lastname: de Wildt
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000293:injuries; D008722:Methods; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009426:Netherlands; D009569:Nitric Oxide / Q000276:immunology* / Q000502:physiology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D037342:Pertussis Toxin / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D010567:Pertussis Vaccine / Q000592:standards; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D002021:Buffers; D010567:Pertussis Vaccine; D010656:Phenylephrine; D009569:Nitric Oxide; D012701:Serotonin; D011189:Potassium Chloride; D006632:Histamine; D037342:Pertussis Toxin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine