title: Histamine-induced biphasic macromolecular leakage in the microcirculation of the conscious hamster: evidence for a delayed nitric oxide-dependent leakage.
abstract: 1. Late effects (up to 3 h) of intravenously-injected histamine on FITC-dextran extravasation were investigated in the conscious hamster, by use of computer-assisted image analysis of fluorescence distribution in a microscopic window of dorsal skin fold preparations. This analysis allowed measurement of local (skin) and general (all organs) extravasations caused by a bolus injection of histamine (1 mg kg(-1), i.v.) 2. Histamine doses higher than 0.01 mg kg(-1) caused biphasic local and general extravasations. Initial phases developed fully within 15 min (for local) and 60 min (for general) and were followed by late phases beginning 90 min after histamine injection. Although the initial and late phases of histamine-induced extravasations had differential apparent reactivities to the autacoid, all the effects of histamine on the microcirculation (1 mg kg[-1]) were inhibited by pyrilamine (1 mg kg(-1), i.v.) but not by cimetidine (1 mg kg(-1), i.v.). 3. Pretreatment with N(G)-monomethyl-L-arginine (L-NMMA, 30 mg kg(-1), i.v.) or N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg kg(-1), i.v.) did not affect the initial phases but did prevent the late phases of local and general extravasations triggered by 1 mg kg(-1) histamine. The inhibitory effects of L-NAME were reversed by L-arginine (30 mg kg[-1]) but not by D-arginine (30 mg kg[-1]) according to the enantioselectivity of nitric oxide synthase (NOS). A late NO-mediated venular dilatation occurred in response to plasma histamine. 4. A low dose of aminoguanidine (1 mg kg(-1), i.v.), a selective inhibitor of the inducible isoform of NOS (iNOS), mimicked the inhibitory effects of L-NAME on the late phases of histamine-induced macromolecular extravasations and venular dilatation. 5. Pretreatment with dexamethasone (1 mg kg(-1), i.v.) prevented both the initial and late phases of histamine-induced extravasations. Fucoidan (1 or 25 mg kg(-1), i.v.) prevented the late phases without affecting initial phases, consistent with a role for leukocytes adhesion in the development of the late NO-mediated effects of histamine. 6. We conclude that intravenous injection of histamine triggers a biphasic inflammatory cascade via initial activation of H1 receptors which induces a late NO-mediated PMN-dependent extravasation process.
authors.affiliation: Service de Pharmacologie, Laboratoire Innothéra, Arcueil, France.
authors.forename: G
authors.initials: G
authors.lastname: Gimeno
authors.forename: P H
authors.initials: PH
authors.lastname: Carpentier
authors.forename: S
authors.initials: S
authors.lastname: Desquand-Billiald
authors.forename: R
authors.initials: R
authors.lastname: Hanf
authors.forename: M
authors.initials: M
authors.lastname: Finet
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D011134:Polysaccharides / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D011134:Polysaccharides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone; D006632:Histamine; C007789:fucoidan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester