Altered alpha adrenergic vasoresponsiveness in a non-cirrhotic portal hypertension model of E. coli injection.

Rizvi, Moattar Raza; Omanwar, Swati; Fahim, Mohammad; Sarin, Shiv Kumar

Background and Aim: Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamic circulation in cirrhosis. Animal models of cirrhosis and portal vein ligation have helped in our understanding of portal hypertension. The etiopathogenesis of non-cirrhotic portal fibrosis (NCPF), a common cause of portal hypertension, is still poorly understood. The aim of this study was to investigate the pathophysiology of NCPF in a rabbit model. Methods: An indwelling cannula was inserted into the gastrosplenic vein of rabbits. Animals were randomly injected with saline (Group I, n = 13) or lipopolysaccharide (Group II, n = 13) from heat killed Escherichia coli at 0, 1, 2, 7, 14 and 28 days. Portal pressure was measured at 3 months and vasoresponsiveness studied in isolated aortic rings in intact and in endothelium-denuded tissues from both groups. Results: In all group II compared with group I animals, the splenic weight (0.89 ± 0.16 vs 0.62 ± 0.1 g, P −4 mol/L as compared to 2.85 ± 0.33 g tension in Group I ( P < 0.05). Endothelium denudation of aortic rings had no effect on reduced reactivity in Group II animals. Acetylcholine induced an increase in vasorelaxation at lower concentrations in preconstricted aortic rings in Group II compared to Group I animals, but this decreased in higher concentrations. Nifedipine produced comparable vasodilatation in preconstricted rings in both the groups of animals. Conclusions: Repeated injection of lipopolysaccharide into the gastrosplenic vein leads to the development of portal hypertension. This non-cirrhotic model of portal hypertension is characterized by generalized arterial hyporeactivity to vasoconstrictors akin to other models of portal hypertension.

PORTAL hypertension; ESCHERICHIA coli; CIRRHOSIS of the liver; PATHOLOGICAL physiology; VASOCONSTRICTORS

Journal of Gastroenterology & Hepatology, 2007, Vol 22, Issue 6, p870

0815-9319

Academic Journal

10.1111/j.1440-1746.2006.04440.x