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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Role of shear stress in aortic eNOS up-regulation in rats with biliary cirrhosis.

BACKGROUND & AIMS: In rats with portal vein stenosis, the initial cause of aortic nitric oxide (NO) overproduction might be overactivation of endothelial NO synthase (eNOS) related to increased shear stress. Cardiac output is higher in cirrhosis than in extrahepatic portal hypertension. The aims of this study were to evaluate the role of shear stress, vascular endothelial growth factor (VEGF), and cytokines in aortic eNOS up-regulation in rats with biliary cirrhosis and to compare these results with those in rats with portal vein stenosis. METHODS: NOS activities, NOS protein, heat shock protein (Hsp) 90, and VEGF expressions were studied in rat aortas. Propranolol was administered to rats with cirrhosis to reduce cardiac output and thus shear stress. RESULTS: In cirrhotic rats, the aortic eNOS protein was 3.0 and 1.7 times higher than in control and portal vein-stenosed rats, respectively. In cirrhotic rats, the Hsp90 content was 3.2 and 2.2 times higher than in control and portal vein-stenosed rats, respectively. Propranolol decreased NOS activity by 47% and eNOS and Hsp90 expression by 75% and 72%, respectively. Aortic VEGF expression was decreased in cirrhotic rats. VEGF-induced stimulation of NOS activity was greater in aortas from control rats than in aortas from portal vein-stenosed or cirrhotic rat aortas. eNOS expression was up-regulated after VEGF incubation. After lipopolysaccharide administration, eNOS expression did not change in portal vein-stenosed or cirrhotic rats. CONCLUSIONS: This study shows that in aortas from rats with biliary cirrhosis, systemic vasodilation depends mainly on eNOS up-regulation related to shear stress.[1]

References

  1. Role of shear stress in aortic eNOS up-regulation in rats with biliary cirrhosis. Tazi, K.A., Barrière, E., Moreau, R., Heller, J., Sogni, P., Pateron, D., Poirel, O., Lebrec, D. Gastroenterology (2002) [Pubmed]
 
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