Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats.

AIM To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase(eNOS) expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 (Hsp90), as well as by the modifications of calmodulin binding to eNOS. METHODS Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats. RESULTS Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length (and the severity) of the disease. Because co-immunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast, cirrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity. CONCLUSION In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide (NO) production is significantly decreased by two mechanisms: a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.