Effect of increased hepatic platelet activating factor and its receptor portal hypertension in CCl4-induced liver cirrhosis.
OBJECTIVE
To evaluate the changes in hepatic platelet activating factor (PAF) and its receptors and their effect on portal pressure of cirrhotic rats induced by CCl4.


METHODS
A model of liver cirrhosis was replicated in rats by intra-peritoneal injection of CCl4 for 8 wk. We determined the effect of hepatic PAF and its receptor level on portal and arterial pressure by EIA, saturation binding and RT-PCR technique.


RESULTS
Compared to control rats, cirrhotic rats had higher hepatic PAF levels and output as well as higher plasma PAF levels (P<0.01, P<0.01, P<0.05, respectively). Both hepatic PAF receptor mRNA levels and PAF binding were nearly 3-fold greater in cirrhotic rats (P<0.01). Portal injection of PAF (1 g/kg WT) increased the portal pressure by 22% and 33% in control and cirrhotic rats, respectively. In contrast, the arterial pressure was decreased in the both groups (54% in control rats and 42% in cirrhotic rats). Injection of the PAF antagonist BN52021 (5 mg/kg WT) decreased the portal pressure by 16% in cirrhotic rats but had no effect in the control rats.


CONCLUSIONS
The upregulation of the PAF system contributes to hepatic hemodynamic and metabolic abnormalities in cirrhosis, and the increased release of PAF into the circulation has impacts on the systemic hemodynamics.
Yang
Yong-Ping
YP
Department of Gastroenterology, 302 Hospital of the Chinese PLA, Beijing 100039, China. yongpingyang@hotmail.com
Ma
Xue-Mei
XM
Wang
Chun-Ping
CP
Han
Jun
J
Lu
Yin-Ying
YY
Xiang
Yi
Y
Su
Shu-Hui
SH
Feng
Yong-Yi
YY
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity; D004224:Diterpenes / Q000494:pharmacology; D046934:Ginkgolides; D006975:Hypertension, Portal / Q000209:etiology* / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D008297:Male; D010972:Platelet Activating Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D002251:Carbon Tetrachloride; C045856:ginkgolide B