PAF, rather than histamine, participates in mouse anaphylactic hypotension.
We determined the roles of platelet-activating factor (PAF) and histamine in anaphylactic hypotension in ovalbumin-sensitized anesthetized BALB/c mice. The effects of PAF and histamine on hemodynamic variables were studied by measuring the systemic arterial (Psa), portal venous (Ppv) and central venous (Pcv) pressures. Intravenous PAF evoked a biphasic Psa response, an initial rapid and transient drop followed by marked hypotension, accompanied by a decrease in Pcv. Histamine caused only mild systemic hypotension. Both agents similarly increased Ppv by approximately 4 cm H(2)O at high doses. After an injection of antigen, Psa initially increased slightly and then decreased from the baseline of 94 +/- 1 mm Hg to 46 +/- 1 mm Hg at 10 min after antigen administration, with Pcv decreasing by 2.5 cm H(2)O. Ppv increased by 3.5 cm H(2)O at 5 min after antigen injection. Pretreatment with either CV-6209 (PAF receptor antagonist, 1 mg/kg) or diphenhydramine (histamine H(1) receptor antagonist, 20 mg/kg) significantly attenuated an antigen-induced decrease in Psa. The inhibitory action of CV-6209 was greater than that of diphenhydramine, and the combination of these 2 antagonists almost completely inhibited the anaphylactic hypotension. In contrast, the antigen-induced increase in Ppv was attenuated by CV-6209 alone but augmented by diphenhydramine. It is concluded that anaphylactic hypotension is mainly mediated by PAF and, to a lesser extent, by histamine in anesthetized BALB/c mice.
Shibamoto
Toshishige
T
Department of Physiology II, Kanazawa Medical University, Uchinada, Japan.
Liu
Wei
W
Cui
Sen
S
Zhang
Wei
W
Takano
Hiromichi
H
Kurata
Yasutaka
Y
D000707:Anaphylaxis / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004155:Diphenhydramine / Q000494:pharmacology; D006632:Histamine / Q000276:immunology* / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007022:Hypotension / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D010972:Platelet Activating Factor / Q000276:immunology* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011726:Pyridinium Compounds / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism
D006634:Histamine H1 Antagonists; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D043562:Receptors, G-Protein-Coupled; D011969:Receptors, Histamine H1; C039351:platelet activating factor receptor; C053321:CV 6209; D006632:Histamine; D004155:Diphenhydramine; D010047:Ovalbumin