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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/G762    most recent 00127.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kemp, W. Articles by Krum, H. PubMed PubMed Citation Articles by Kemp, W. Articles by Krum, H.

LIVER AND BILIARY TRACT

Urotensin II modulates hepatic fibrosis and portal hemodynamic alterations in rats

¹Department of Epidemiology and Preventive Medicine, Monash University; Departments of ²Gastroenterology and Hepatology and ⁴Anatomical Pathology, Alfred Hospital; ³Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia

Submitted April 1, 2009 ; accepted in final form July 29, 2009

The influence of circulating urotensin II (UII) on liver disease and portal hypertension is unknown. We aimed to evaluate whether UII executes a pathogenetic role in the development of hepatic fibrosis and portal hypertension. UII was administered by continuous infusion over 4 wk in 20 healthy rats divided into three treatment groups, controls (saline, n = 7), low dose (UII, 1 nmol·kg^–1·h^–1, n = 8), and high dose (UII, 3 nmol·kg^–1·h^–1, n = 5). Hemodynamic parameters and morphometric quantification of fibrosis were assessed, and profibrotic cytokines and fibrosis markers were assayed in hepatic tissue. UII induced a significant dose-dependent increase in portal venous pressure (5.8 ± 0.4, 6.4 ± 0.3, and 7.6 ± 0.7, respectively, P = 0.03). High-dose UII infusion was associated with an increase in hepatic transcript for transforming growth factor-β (P < 0.05) and platelet-derived growth factor-β (P = 0.06). Liver tissue hydroxyproline was elevated in the high-dose group (P < 0.05). No systemic hemodynamic alterations were noted. We concluded that UII infusion elevates portal pressure and induces hepatic fibrosis in normal rats. This response may be mediated via induction of fibrogenic cytokines. These findings have pathophysiological implications in human liver disease where increased plasma UII levels have been observed.

cirrhosis; portal hypertension; liver disease