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

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 (CCl4)-induced acute hepatic injury.

METHODS

Rats were pretreated with CCl4 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 NG-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 CCl4, 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 CCl4-treated rats. Plasma nitrite/nitrate levels and hepatic NOS activity were increased significantly by CCl4 treatment. Inducible NOS mRNA was detected in CCl4-treated rats but not in the controls.

CONCLUSIONS

The results of this study suggest that the increased hepatic arterial blood flow in CCl4-induced acute hepatic injury is mediated by excessive NO production and up-regulated by inducible NOS, which plays a role in reducing hepatic injury.