Effects of nitric oxide on ammonia decomposition by hepatocytes under shear stress

Nitric oxide (NO) and shear stress modulates hepatocyte functions, including ammonia metabolism. This study investigated the simultaneous effects of NO and shear stress on hepatocyte functions. We developed a cell culture device to simultaneously apply NO and shear stress to hepatocytes, and measured changes in ammonia decomposition by hepatocytes in response to changes in NO concentration and shear stress. NO was supplied directly to cells at a constant rate at 0, 0.5, 5, and 25 ppm, and shear stress was either applied at 0.6 Pa or not (static culture). Ammonia decomposition in static culture was higher under all NO loads compared with 0 ppm NO, and was highest under 0.5 ppm NO and decreased under higher NO loads. In the absence of NO load, ammonia decomposition under shear stress was approximately double that in static culture. Under the simultaneous application of NO and shear stress load, ammonia decomposition under 0.5 ppm NO was approximately twice as high as under 0 ppm NO, but was almost the same under 25 ppm NO as under 0 ppm NO. These results indicate that both NO and shear stress enhance ammonia decomposition although the enhancement depends on the NO concentration in their immediate surroundings.