title: Constitutive nitric oxide synthase inhibition combined with histamine and serotonin receptor blockade improves the initial ovalbumin-induced arterial hypotension but decreases the survival time in brown norway rats anaphylactic shock.
abstract: Anaphylactic shock accidents after allergen exposure are frequent. After immunization with ovalbumin (OVA), a common dietary constituent, we evaluated the efficacy of pretreatment with histamine-receptor or serotonin-receptor blockers administered alone or in combination with a nitric oxide synthase inhibitor (L-NAME) on OVA-induced anaphylactic shock in Brown Norway rats. Animals were allocated to the following groups (n = 6 each): control (0.9% saline); diphenydramine (15 mg kg(-1)); cimetidine (20 mg kg(-1)); diphenydramine + cimetidine; dihydroergotamine (50 microg kg(-1)); diphenydramine + cimetidine + dihydroergotamine; L-NAME (100 mg/kg) alone or associated with diphenydramine, cimetidine, diphenydramine + cimetidine, dihydroergotamine, or diphenydramine + cimetidine + dihydroergotamine. Mean arterial blood pressure (MABP), heart rate (HR), and survival time were monitored for 60 min following treatment. The shock was initiated with i.v. OVA. The MABP drop after i.v. OVA was worsened by diphenydramine and was modestly attenuated by cimetidine, dihydroergotamine, or both together. L-NAME potentiated slightly the effects of cimetidine and dihydroergotamine by lessening the initial MABP decrease, but this transient effect was not sufficient to prevent the final collapse or to improve survival time. Decreased vasodilatory (prostaglandins E2), increased vasoconstrictory (thromboxane B2) prostaglandins, and unchanged leukotriene C4 concentrations were contributory to the overall hemodynamic changes. Thus, the combined blockade of vasodilator mediators (histamine, serotonin, and nitric oxide) slowed the MABP drop in anaphylactic shock, but did not improve survival. More studies are needed to understand these discordant effects.
authors.affiliation: Experimental Nephrology Laboratory, Vandoeuvre les Nancy, 54505, France.
authors.forename: Abdelouahab
authors.initials: A
authors.lastname: Bellou
authors.forename: Henri
authors.initials: H
authors.lastname: Lambert
authors.forename: Pierre
authors.initials: P
authors.lastname: Gillois
authors.forename: Chantal
authors.initials: C
authors.lastname: Montémont
authors.forename: Philippe
authors.initials: P
authors.lastname: Gerard
authors.forename: Eliane
authors.initials: E
authors.lastname: Vauthier
authors.forename: Jean
authors.initials: J
authors.lastname: Sainte-Laudy
authors.forename: Dan
authors.initials: D
authors.lastname: Longrois
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Guéant
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Mallié
mesh_terms: D000707:Anaphylaxis / Q000401:mortality*; D000818:Animals; D001158:Arteries / Q000473:pathology*; D002927:Cimetidine / Q000494:pharmacology; D004087:Dihydroergotamine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D007022:Hypotension / Q000378:metabolism*; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010047:Ovalbumin / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D011914:Rats, Inbred BN; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors
chemical_list: D015777:Eicosanoids; D004791:Enzyme Inhibitors; D011985:Receptors, Serotonin; D017997:Leukotriene C4; D012701:Serotonin; D004087:Dihydroergotamine; D013929:Thromboxane B2; D002927:Cimetidine; D006632:Histamine; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester