Patients with Viral Cirrhosis K. Mumtaz 1 , S. Ahmed 1 , H. Ali Shah 1 , S. Hamid 1 , W. Jafri 1 Background and Aims: Increased nitric oxide (NO) production is incriminated in the pathogenesis of arterial vasodilation and hyperdynamic circulatory state in non cirrhotic models of portal hypertension (PHT). We investigated the relative roles of constitutive NOS (eNOS) and inducible NOS (iNOS) isoforms in the development of rabbit models of endotoxemia induced portal hypertension (EIPHT) Methods: EIPHT was induced by chronic injection of lipopolysaccharide via an indwelling cannula placed in the gastrosplenic vein of rabbit and maintained for 6 months. The concentration of NO, expression of NOS (eNOS and iNOS) mRNA and protein was measured in EIPHT and sham operated control animals. Results: Rabbits with EIPHT compared with controls had raised portal pressure (in mmHg-14.34±1.78 vs 6.30±0.60;p<0.05;1mo; 14.91±0.56 vs 7.04±0.42; p<0.05, 3mo; 19.8±3.10, vs 10.2±4.80;p<0.05), arterial hypotension (in mmHg-65.40±3.2 vs 80.04±1.40, p<0.05, 1mo; 62.90±5.40 vs 76.05±2.60,p<0.05, 3mo; 65.85±2.50 vs 79.1±5.10, p<0.05,6mo), splenomegaly (in g-0.92±0.14 vs 0.60±0.13,1mo; 0.90±0.16 vs 0.62±0.04, 3mo; 0.97±0.12 vs 0.67±0.07, 6mo), normal liver functions and preserved hepatic architecture at 1,3 and 6 mo. Serum levels of NO2 as well as the NO3 were significantly elevated in EIPHT rabbits as compared to the controls. The expression of eNOS, at the level of mRNA, was significantly increased in EIPHT rabbits consistent with increased levels of expression of iNOS as compared to the controls. The eNOS but not iNOS protein expression was elevated in EIPHT than control rabbits. Conclusion: Vascular dysfunction in the splanchnic circulation during the development of endotoxemia induced portal hypertension is predominantly characterized by eNOS and partly by iNOS gene up-regulation.