Increased expression of endothelin receptors in human cirrhosis —Relationship with splanchnic hemodynamics

Abstract

The purpose of the present study was to assess the correlation that likely exists among increased portal pressure (P_p), portal blood flow quantity (Q_p) and ET_A and ET_B receptor mRNA expression in human cirrhosis.In situ hybridization and reverse-transcription polymerase chain reactions (RT-PCR) were performed to determine the expression of ET_A and ET_B receptor mRNA in liver tissues from traumatic subjects (n=10) and cirrhotic patients (n=15) in whom hepatic hemodynamic values were measured. The expression of the two transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from traumatic subjects. It has shown that ET_A receptor mRNA predominantly located in hepatic stellate cells (HSCs) and vascular smooth muscle cells of intrahepatic arteries and portal veins, ET_B receptor mRNA in HSCs, sinusoidal endothelial cells and Kuppfer cells. There was a highly significant direct relationship between ET_A and ET_B receptor mRNA and P_p and Q_p in cirrhotic patients. It suggests that liver paracrine endothelin system may be overactivated in human cirrhosis accompanied with increased expression of ET_A and ET_B receptor mRNA which may play an important role in the pathogenesis and maintenance of splanchnic hyperdynamics.

Keywords

endothelin receptors / cirrhosis / portal hypertension / hemodynamics / gene expression / in situ hybridization / RT-PCR

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