Leukotrienes and cyclooxygenase products mediate anaphylactic venoconstriction in ovalbumin sensitized rat livers.
Hepatic anaphylactic venoconstriction is partly involved in anaphylactic hypotension. We determined the chemical mediators responsible for anaphylaxis-induced segmental venoconstriction in perfused livers isolated from ovalbumin-sensitized rats. Livers were perfused portally and recirculatingly at constant flow with diluted blood. The portal venous pressure (Ppv), hepatic venous pressure (Phv), liver weight and hepatic oxygen consumption were continuously measured. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost) resistances. After antigen injection, both Ppv and Pdo increased, resulting in 5.6- and 1.6-fold increases in Rpre and Rpost, respectively. Liver weight showed a biphasic change of an initial decrease followed by an increase. Hepatic oxygen consumption significantly decreased after antigen. Anaphylaxis-induced increase in Rpre was most extensively inhibited by 38.6% by pretreatment with ONO-1078 (100 microM, a cysteinyl leukotriene receptor-1 antagonist), among all antagonists or inhibitors administrated individually including TCV-309 (20 microM), AA-2414 (10 microM), ketanserin (10 microM) and indomethacin (10 microM). Combined pretreatment with indomethacin and ONO-1078 exerted additive inhibitory effects and attenuated Rpre by 65.8%. However, TCV-309, a platelet activating factor (PAF) receptor antagonist, did not affect the anaphylactic response. In contrast, anaphylaxis-induced increase in Rpost was attenuated only by ONO-1078 combined pretreatment. The antigen-induced changes in liver weight and hepatic oxygen consumption were attenuated significantly when hepatic venoconstriction was attenuated. It is concluded that cysteinyl leukotrienes and cyclooxygenase products, but not PAF, are mainly involved in anaphylaxis-induced pre-sinusoidal constriction in isolated perfused rat livers.
Cui
Sen
S
Department of Physiology 2, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan.
Shibamoto
Toshishige
T
Takano
Hiromichi
H
Zhang
Wei
W
Kurata
Yasutaka
Y
D000707:Anaphylaxis / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000502:physiology*; D008099:Liver / Q000098:blood supply / Q000503:physiopathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014690:Venous Pressure / Q000187:drug effects
D000941:Antigens; D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D010047:Ovalbumin; D011451:Prostaglandin-Endoperoxide Synthases; C047681:pranlukast; D007213:Indomethacin