Role of prostanoids and nitric oxide inhibition in rats with experimental hepatic fibrosis

Nitric oxide (NO) and prostaglandins have been proposed as vasodilator subs tances involved in peripheral vasodilatation characteristic of the liver ci rrhosis. A link between NO and prostanoids has been suggested. The present study investigated the effect of simultaneous blockade of both, NO synthase (NOS) and cyclooxigenase (COX) in sham-operated (SO), or rats with bile-du ct ligation (BDL) in the development of liver fibrosis. Animals were distri buted in two groups SO (n=15) or BDL (n=15). Treatments (5 days) started th ree weeks after surgical procedure. Both, SO and BDL animals were treated w ith indomethacin (INDO) (5 mg/kg/day) alone, with N-G-nitro-L-arginine-meth yl-ester (NAME) (4 mg/kg/day) alone or with INDO and NAME combination at th e same doses. At the end of follow-up body weight, packed cell volume, mean arterial blood pressure (MAP) and heart rate were measured. Liver tissue w as processed for histological studies. In this study, BDL animals showed a decreased MAP. Treatment with L-NAME in BDL rats increased MAP. The chronic COX inhibition alone did not play an important role in the haemodynamic ch anges. The BDL produced a loss of hepatic structure, with ductular metaplas ia that occupied the greater part of the hepatic parenchyma. Also, an impor tant degree of fibrosis was observed. Both NO and PG synthesis inhibitors, alone or in combination, induced enhancing collagen fiber deposition in the hepatic parenchyma. These findings support the notion that the interaction between the NOS and COX pathways should be relevant in hepatic cirrhosis i n which both NOS and COX are induced.