Nitric oxide increases hepatic arterial blood flow in rats with carbon tetrachloride–induced acute hepatic injury

Abstract

Background & Aims: Little is known about the changes in hepatic blood flow associated with acute hepatic injury. The aim of this study was to investigate the effect of nitric oxide (NO) on hepatic blood flow and the severity of hepatic injury in rats with carbon tetrachloride (CCl 4)-induced acute hepatic injury. Methods: Rats were pretreated with CCl 4 to induce acute hepatic injury. Hepatic blood flow was measured using a radioactive microsphere method. The role of NO in the regulation of hepatic blood flow and the severity of hepatic injury was investigated by administering N G -nitro- L-arginine ( L-NNA) and aminoguanidine (AG). Plasma nitrite/nitrate levels, hepatic NO synthase (NOS) activity, and expression of hepatic NOS messenger RNA (mRNA) were measured, and histological examinations were performed. Results: Hepatic arterial and portal venous blood flow was increased significantly by CCl 4, without any change in mean arterial pressure or cardiac output. L-NNA and AG dose-dependently decreased hepatic arterial blood flow, with the highest dose resulting in complete blockade of hepatic arterial dilation, but failed to change portal venous blood flow. Histologically, administration of AG aggravated the hepatic injury in CCl 4-treated rats. Plasma nitrite/nitrate levels and hepatic NOS activity were increased significantly by CCl 4 treatment. Inducible NOS mRNA was detected in CCl 4-treated rats but not in the controls. Conclusions: The results of this study suggest that the increased hepatic arterial blood flow in CCl 4-induced acute hepatic injury is mediated by excessive NO production and up-regulated by inducible NOS, which plays a role in reducing hepatic injury. GASTROENTEROLOGY 1999;117:173-180