A hyperdynamic circulatory state frequently is ob-Portal hypertension accompanied by anatomic or served in portal hypertension with liver failure or exten-functional portal-systemic shunting very often is assosive portal-systemic shunting. Tumor necrosis factor a ciated with a hyperdynamic circulatory state. The so-(TNF) causes marked hypotension in mammals by in-called hyperdynamic circulatory syndrome (HCS) is ducing nitric oxide synthesis and has been shown to play characterized by generalized vasodilatation with a dea role in the development of the hemodynamic changes crease in mean arterial pressure and systemic vascular observed in portal hypertension. Thalidomide selec-resistance and an increase in cardiac output and retively inhibits TNF production by enhancing messenger gional blood flows. Although the cause of this syndrome RNA degradation. We investigated the systemic and poris still a matter of controversy, it seems that vasodilatatal hemodynamic effects of thalidomide in a prehepatic model of portal hypertension and evaluated whether tion, induced by increased activity of endothelial-indesuppressing TNF synthesis decreases NO production. pendent and endothelial-dependent vasodilators, initiPortal hypertension was induced by partial ligation of ates the hyperdynamic state. 1 the portal vein (PVL). Animals received thalidomide (T)Various substances have been proposed as mediators (50 mg/kg/d) / water or water alone (W), orally, daily for of the HCS. Recently, a role for endogenous nitric oxide 2 days before and 13 days after PVL operation, at which in the regulation of blood flow and vascular tone of the time hemodynamic studies were performed and TNF systemic and splanchnic circulations in portal hypertenplasma levels were obtained. Sham-operated animals sion has been suggested by several in vivo and in vitro were studied identically. In an additional group of PVL animals, 24-hour urinary excretion of NO 0 2 and NO 0 3 was studies, implying that excessive synthesis of NO could measured during treatment. PVL animals receiving T be responsible for these circulatory abnormalities. 2,3 presented with a significantly higher mean arterial presTumor necrosis factor a (TNF), a 17-kd, mononusure and systemic vascular resistance and significantly clear-derived cytotoxic protein, causes marked hypolower portal pressure, TNF plasma levels, and 24-hour tension in mammals. 4 inhibiting TNF synthesis and decreasing NO synthesis,

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