Nitric oxide and vascular remodeling modulate hepatic arterial vascular resistance in the isolated perfused cirrhotic rat liver

Background/Aims Hepatic arterial resistance is modulated by the hepatic arterioles but the role of NO and vascular remodeling in hepatic arterial resistance in cirrhosis is unknown. Methods Cirrhosis was induced by CCl4 or BDL. Using a bivascular liver perfusion dose-responses curves to methoxamine were obtained from the hepatic artery in absence and presence of L-NMMA. Lumen-diameter, wall thickness and number of smooth muscle nuclei were quantitated in the arteries using image analysis. Results Hepatic arterial resistance and the response to methoxamine were lower in cirrhosis compared to controls (p 0.04) and lower in BDL compared to CCl4 (p 0.01). L-NMMA increased the response to methoxamine in CCl4 (p = 0.002) and BDL (p = 0.05) but corrected the response only in CCl4 (p = n.s. vs. control). Wall thickness and the number of smooth muscle nuclei were significantly smaller in cirrhosis compared to controls (p < 0.05) and the number of nuclei was also lower in BDL compared to CCl4 (p = 0.005). Conclusions NO is the main modulator of hepatic arterial resistance in CCl4 but not in BDL. Intrahepatic arterial remodeling is present in both cirrhotic models but is greater in BDL. This indicates a larger role of structural changes in the control of hepatic arterial resistance in BDL.