Aim: 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.
Conclusion: 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.