Altered alpha adrenergic vasoresponsiveness in a non-cirrhotic portal hypertension model of E. coli injection.
OBJECTIVE
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 < 0.05) and the portal pressure (14.99 +/- 0.56 vs 7.04 +/- 0.42 mmHg, P < 0.05) were higher at 3 months. The group II animals showed reduced responsiveness to phenylephrine showing maximal contraction of 1.25 +/- 0.08 at 10(-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.
Rizvi
Moattar Raza
MR
Department of Gastroenterology, G. B. Pant Hospital, University of Delhi, New Delhi, India.
Omanwar
Swati
S
Fahim
Mohammad
M
Sarin
Shiv Kumar
SK
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli; D005355:Fibrosis; D006975:Hypertension, Portal / Q000209:etiology* / Q000503:physiopathology*; D007267:Injections; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects
D008070:Lipopolysaccharides; D010656:Phenylephrine; D000109:Acetylcholine