Effects of platelet-activating factor and thromboxane A2 on isolated perfused guinea pig liver.
Lipid mediators, thromboxane A2 (TxA2) and platelet-activating factor (PAF), are potent vasoconstrictors, and have been implicated as mediators of liver diseases, such as ischemic-reperfusion injury. We determined the effects of a TxA2 analogue (U-46619) and PAF on the vascular resistance distribution and liver weight (wt) in isolated guinea pig livers perfused with blood via the portal vein. The sinusoidal pressure was measured by the double occlusion pressure (P(do)), and was used to determine the pre- (R(pre)) and post-sinusoidal (R(post)) resistances. U-46619 and PAF concentration-dependently increased the hepatic total vascular resistance (R(t)). The minimum concentration at which significant vasoconstriction occurs was 0.001 microM for PAF and 0.1 microM for U-46619. Moreover, the concentration of U-46619 required to increase R(t) to the same magnitude is 100 times higher than PAF. Thus, the responsiveness to PAF was greater than that to U-46619. Both agents increased predominantly R(pre) over R(post). U-46619 caused a sustained liver weight loss. In contrast, PAF also caused liver weight loss at lower concentrations, but it produced liver weight gain at higher concentrations (2.5 +/- 0.3 per 10g liver weight at 1 microM PAF), which was caused by substantial post-sinusoidal constriction and increased P(do). In conclusion, both TxA2 and PAF contract predominantly the pre-sinusoidal veins. TxA2 causes liver weight loss, while PAF at high concentrations increases liver weight due to substantial post-sinusoidal constriction in isolated guinea pig livers.
Ruan
Zonghai
Z
Department of Physiology, Division 2, Kanazawa Medical University, Uchinada 920-0293, Japan.
Shibamoto
Toshishige
T
Shimo
Tomohiro
T
Koizumi
Tomonobu
T
Tsuchida
Hideaki
H
Kurata
Yasutaka
Y
Ogura
Toshitsugu
T
Kubo
Keishi
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007260:Infusion Pumps; D008099:Liver / Q000098:blood supply* / Q000503:physiopathology*; D008102:Liver Circulation / Q000187:drug effects; D008107:Liver Diseases / Q000503:physiopathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010972:Platelet Activating Factor / Q000008:administration & dosage* / Q000378:metabolism; D011169:Portal Vein / Q000503:physiopathology; D015427:Reperfusion Injury / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000008:administration & dosage* / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000378:metabolism
D010972:Platelet Activating Factor; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid