Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/18648
Title: Superoxide dismutase gene transfer reduces portal pressure in ccl4 cirrhotic rats with portal hypertension.
Author: Laviña Siemsen, Bàrbara
Gracia-Sancho, Jorge
Rodríguez-Vilarrupla, A.
Chu, Y.
Heistad, D. D.
Bosch i Genover, Jaume
García Pagán, Juan Carlos
Keywords: Cirrosi hepàtica
Hipertensió portal
Transformació genètica
Superòxid dismutasa
Hepatic cirrhosis
Portal hypertension
Genetic transformation
Superoxide dismutase
Issue Date: 2009
Publisher: BMJ Group
Abstract: Background: Increased intrahepatic vascular tone in cirrhosis has been attributed to a decrease of hepatic nitric oxide (NO) secondary to disturbances in the post-translational regulation of the enzyme eNOS. NO scavenging by superoxide (O2−) further contributes to a reduction of NO bioavailability in cirrhotic livers. Aim: To investigate whether removing increased O2− levels could be a new therapeutic strategy to increase intrahepatic NO, improve endothelial dysfunction and reduce portal pressure in cirrhotic rats with portal hypertension. Methods: Adenoviral vectors expressing extracellular superoxide dismutase (SOD) (AdECSOD) or β-galactosidase (Adβgal) were injected intravenously in control and CCl4-induced cirrhotic rats. After 3 days, liver O2− levels were determined by dihydroethidium staining, NO bioavailability by hepatic cGMP levels, nitrotyrosinated proteins by immunohistochemistry and western blot, and endothelial function by responses to acetylcholine in perfused rat livers. Mean arterial pressure (MAP) and portal pressure were evaluated in vivo. Results: Transfection of cirrhotic livers with AdECSOD produced a significant reduction in O2− levels, a significant increase in hepatic cGMP, and a decrease in liver nitrotyrosinated proteins which were associated with a significant improvement in the endothelium-dependent vasodilatation to acetylcholine. In addition, in cirrhotic livers AdECSOD transfection produced a significant reduction in portal pressure (17.3 (SD 2) mm Hg vs 15 (SD 1.6) mm Hg; p<0.05) without significant changes in MAP. In control rats, AdECSOD transfection prevents the increase in portal perfusion pressure promoted by an ROS-generating system. Conclusions: In cirrhotic rats, reduction of O2− by AdECSOD increases NO bioavailability, improves intrahepatic endothelial function and reduces portal pressure. These findings suggest that scavenging of O2− might be a new therapeutic strategy in the management of portal hypertension.
Note: Reproducció digital del document publicat a: http://dx.doi.org/10.1136/gut.2008.149880
It is part of: Gut, 2009, vol. 58, núm. 1, p. 118-125
Related resource: http://dx.doi.org/10.1136/gut.2008.149880
URI: http://hdl.handle.net/2445/18648
ISSN: 0017-5749
Appears in Collections:Articles publicats en revistes (Medicina)

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