[Influence of platelet activating factor and its antagonist on portal hypertension associated with liver cirrhosis: an experiment with rats].
OBJECTIVE
To investigate the influence of platelet activating factor (PAF) and its antagonist BN52021 on portal hypertension associated with liver cirrhosis.


METHODS
Ten SD rats were injected intraperitoneally with carbon tetrachloride to establish a liver cirrhosis model and 10 rats were injected with olive oil as controls. The concentrations of PAF in the blood and liver was examined by rapid (3)H-PAF scintillation proximity assay and the hepatic PAF binding capacity was examined by receptor saturation binding technique. The pressure of portal vein and pressure of femoral artery were measured by intubation method. BN52021 was infused into the portal vein to observe its influence on the blood pressure.


RESULTS
The hepatic PAF levels of the cirrhotic rats was 4.0 ng/g +/- 0.4 ng/g, significantly higher than that of the control rats (2.7 ng/g +/- 0.5 ng/g, P < 0.01). The hepatic efflux PAF level of the cirrhotic rats was 6.3 ng/g +/- 0.6 ng/g, significantly higher than that of the control rats (3.4 ng/g +/- 0.6 ng/g, P < 0.01). The hepatic output PAF levels of the cirrhotic rats was 1.0 ng/g +/- 0.6 ng/g, significantly lower than that of the control rats (0.3 ng/g +/- 0.5 ng/g, P < 0.01). The maximum PAF binding capacity of the cirrhotic rats was 2.8 +/- 0.21 fmol/microg protein, significantly higher than that of the control rats (0.9 +/- 0.06 fmol/microg protein, P < 0.01). However, the receptor affinity was not significantly different between these 2 groups. The portal pressure of the cirrhotic rats was 12.2 mm Hg +/- 0.7 mm Hg, significantly higher than that of the control rats (5.3 mm Hg +/- 0.6 mm Hg, P < 0.01). The femoral arterial pressure of the cirrhotic rats was 82 mm Hg +/- 10 mm Hg, significantly lower than that of the control rats (114 mm Hg +/- 9 mm Hg, P < 0.01). Infusion of PAF via the portal vein increased the portal pressure from 12.1 mm Hg +/- 0.6 mm Hg with an increase of 32% (P < 0.01) in the cirrhotic rats, and from 7.7 mm Hg +/- 0.8 mm Hg with an increase of 23%. The PAF response of the cirrhotic rats was 4.1 mm Hg +/- 1.0 mm Hg (227%), significantly higher than that of the control rats (1.8 mm Hg +/- 0.3 mm Hg, P < 0.01). The femoral artery pressure decreased from 82 mm Hg +/- 10 mm Hg to 48 mm Hg +/- 4 mm Hg (P < 0.01) in the cirrhotic rats, and from 114 mm Hg +/- 9 mm Hg to 52 mm Hg +/- 4 mm Hg (P < 0.01). After portal infusion of BN52021 the portal pressure decreased from 14.6 mm Hg +/- 1.6 mm Hg to 12.3 mm Hg +/- 0.8 mm Hg (P < 0.05) with a decrease of 16%, however, did not significantly influenced the femoral arterial pressure in the cirrhotic rats, and did not significantly influenced the portal pressure and femoral arterial pressure in the control rats.


CONCLUSIONS
The increased hepatic PAF synthesis in cirrhotic is the major source of elevated circulating PAF It upregulates the hepatic hemodynamics that contributes to portal hypertension. The increased portal pressure by endogenous PAF can be decreased to a certain extent by BN52021 which may be used in treatment of portal hypertension.
Wang
Chun-ping
CP
Department of No. 9 Internal Medicine, Hospital No. 302 of Chinese People's liberation Army, Beijing 100039, China.
Han
Jun
J
Ma
Xue-mei
XM
Dong
Kun
K
Xiang
Yi
Y
Su
Shu-hui
SH
Feng
Yong-yi
YY
Yang
Yong-ping
YP
D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D046934:Ginkgolides / Q000008:administration & dosage / Q000494:pharmacology; D006975:Hypertension, Portal / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D007275:Injections, Intravenous; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D002251:Carbon Tetrachloride; C045856:ginkgolide B