title: Mouse anaphylactic shock is caused by reduced cardiac output, but not by systemic vasodilatation or pulmonary vasoconstriction, via PAF and histamine.
abstract: OBJECTIVE
  Systemic anaphylaxis is life-threatening, and its pathophysiology is not fully clarified. Mice are frequently used for experimental study on anaphylaxis. However, the hemodynamic features and mechanisms of mouse anaphylactic hypotension remain unknown. Therefore, we determined mechanisms of systemic and pulmonary vascular response to anaphylactic hypotension in anesthetized BALB/c mice by using receptor antagonists of chemical mediators.
  
  
  METHODS
  Anaphylaxis was actively induced by an intravenous injection of the ovalbumin antigen into open-chest artificially ventilated sensitized mice. Mean arterial pressure (MAP), pulmonary arterial pressure (PAP), left atrial pressure, central venous pressure, and aortic blood flow (ABF) were continuously measured.
  
  
  RESULTS
  In sensitized control mice, MAP and ABF showed initial, transient increases, followed by progressive decreases after the antigen injection. Total peripheral resistance (TPR) did not decrease, while PAP initially and transiently increased to 18.5±0.5mmHg and pulmonary vascular resistance (PVR) also significantly increased. The antigen-induced decreases in MAP and ABF were attenuated by pretreatment with either a platelet-activating factor (PAF) receptor antagonist, CV6209, or a histamine H1 receptor antagonist, diphenhydramine, and were abolished by their combination. Diphenhydramine augmented the initial increases in PAP and PVR, but did not affect the decrease of the corresponding MAP fall. The antagonists of either leukotriene C4 or serotonin, alone or in combination with CV6209, exerted no significant effects.
  
  
  CONCLUSIONS
  Mouse anaphylactic hypotension is caused by a decrease in cardiac output but not vasodilatation, via actions of PAF and histamine. The slight increase in PAP is not involved in mouse anaphylactic hypotension.
authors.affiliation: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan; Department of Colorectal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, China.
authors.forename: Mofei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. Electronic address: shibamo@kanazawa-med.ac.jp.
authors.forename: Toshishige
authors.initials: T
authors.lastname: Shibamoto
authors.affiliation: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanida
authors.affiliation: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Yuhichi
authors.initials: Y
authors.lastname: Kuda
authors.affiliation: Department of Physiology II, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kurata
mesh_terms: D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D062186:Arterial Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology*; D004155:Diphenhydramine / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D006632:Histamine / Q000378:metabolism*; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011726:Pyridinium Compounds / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C053321:CV 6209; D006632:Histamine; D004155:Diphenhydramine; D010047:Ovalbumin
keywords: Anaphylaxis; Pulmonary arterial pressure; Pulmonary vascular resistance; Total peripheral resistance