MORITAKA Go'ro, SHINGO TSIJJI,' TOMOKI MICHIDA,' SHENG-SONG CHEN,' TORU KASHIWAGI,'
The purpose of this study was to evaluate the role of endothelin-1 in modulating hepatic microcirculation and liver damage. Rats were infused with endothelin-1 at doses ranging from 30 to 1,000 pmolkg over 1 min through an indwelling cannula placed in the portal vein. In control rats, saline solution was infused at the same rate. Alterations in hepatic microcirculation were measured with an in uiuo microscopy system. Serum lactate dehydrogenase activity, an indicator of hepatic damage, was measured 1 hr after endothelin-1 infusion. Immediately after infusion of endothelin-1, we noted a rapid increase in portal pressure, which remained increaaed for up to 30 min after endothelin-1 infusion. In contrast, systemic blood pressure remained unchanged, even at 1,000 pmolkg of endothelin-1. Sinuaoidal width was reduced and sinusoidal erythrocyte velocity was diminished in a dose-dependent manner. Oxygen saturation of blood in sinusoids was decreased in a dose-dependent manner, reaching values around 40% of control with 1,000 pmolkgendothelin-1. The degree of decrease in oxygen saturation of blood in sinusoids had an excellent correlation with the calculated blood flow in the liver tiseue. Serum lactate dehydrogenase levels were three to four times control values when endothelin-1 was administered at 1,000 pmolkg. Thus endothelin-1 decreased hepatic tissue oxygenation associated with sinusoidal vasoconstriction. At high concentrations of endothelin-1, this decrease results in hepatocellular damage. (FIEPATOLOGY 1994;19: 155-161.) Endothelin-1, a 21 amino acid peptide derived from vascular endothelial cells, produces prolonged constriction of mammalian blood vessels (1). This endogenous peptide may be involved in physiological regulation of vascular tone and in the pathophysiologic aspects of various vascular disorders (2, 3).