Hepatic effects of influxed endothelin-1 from portal vein: in situ portal vein infusion model using dogs

Background/Purpose

Endothelin-1 is a potent vasoconstrictor formed by vascular endothelium. This study was designed to investigate the hepatic effect of endothelin-1 produced by portal vascular endothelium.

Methods

Portal venous pressure, portal venous flow, hepatic arterial flow, tissue blood flow, and tissue oxygen pressure were measured during portal vein endothelin-1 infusion in dogs at rates of 1.0 to 5.0?ng/kg per minute. Sinusoidal width during maximal infusion was determined morphometrically. Serum concentrations of mitochondrial glutamic oxaloacetic transaminase and endothelin-1 in portal and hepatic venous blood were also measured.

Results

Intraportal endothelin-1 infusion dose-dependently increased portal venous pressure and reduced portal venous and hepatic arterial blood flow. Tissue blood flow and oxygen pressure also decreased. Endothelin-1 also significantly increased serum mitochondrial glutamic oxaloacetic transaminase and constricted hepatic sinusoids. These changes reversed after completion of infusion.

Conclusions

Intraportal endothelin-1 caused circulatory and histological changes in hepatic sinusoids that may suggest the role of endothelin-1 formed by portal venous bed epithelium.