Involvement of platelet-activating factor and leukotrienes in anaphylactic segmental venoconstriction in ovalbumin sensitized guinea pig livers.
The hepatic anaphylactic venoconstriction is partly involved in anaphylactic hypotension, and is characterized by significant post-sinusoidal constriction and liver congestion in guinea pigs. We determined what chemical mediators are involved in anaphylaxis-induced segmental venoconstriction and liver congestion in perfused livers isolated from ovalbumin sensitized guinea pigs. Livers were perfused portally and recirculatingly at constant flow with diluted blood. 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. An antigen injection increased both the portal vein pressure and Pdo, resulting in 4.1- and 2.3-fold increases in Rpre and Rpost, respectively. Hepatic congestion was observed as reflected by liver weight gain. Pretreatment with TCV-309 (10microM, platelet-activating factor (PAF) receptor antagonist) or ONO-1078 (100microM, human cysteinyl-leukotriene (Cys-LT) receptor 1 antagonist), but not indomethacin (10microM, cyclooxygenase inhibitor), ketanserin (10microM, serotonin receptor antagonist), or diphenhydramine (100microM, histamine H1 antagonist), significantly attenuated this anaphylactic hepatic venoconstriction. Anaphylaxis-induced increases in Rpre and Rpost were significantly inhibited by TCV-309 (by 48%) and ONO-1078 (by 36%), respectively. Combined TCV-309 and ONO-1078 pretreatment exerted additive inhibitory effects on anaphylactic hepatic venoconstriction. Anaphylactic hepatic weight gain was converted to weight loss when post-sinusoidal constriction was attenuated. It is concluded that anaphylaxis-induced pre-sinusoidal constriction is mainly caused by PAF and the post-sinusoidal constriction by Cys-LTs in guinea pig livers.
Shibamoto
Toshishige
T
Department of Physiology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. shibamo@kanazawa-med.ac.jp
Ruan
Zonghai
Z
Cui
Sen
S
Liu
Wei
W
Kurata
Yasutaka
Y
D000818:Animals; D002867:Chromones / Q000494:pharmacology; D006168:Guinea Pigs; D015289:Leukotrienes / Q000502:physiology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D009929:Organ Size; D010047:Ovalbumin / Q000008:administration & dosage*; D010972:Platelet Activating Factor / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D002867:Chromones; D015289:Leukotrienes; D010972:Platelet Activating Factor; D010047:Ovalbumin; C047681:pranlukast