The L-arginine/NO pathway in end-stage liver disease and during orthotopic liver and kidney transplantation : Biological and analytical ramifications

摘要: The L-arginine/nitric oxide (L-Arg/NO) pathway is altered in liver and kidney diseases. However, the status of L-Arg/NO during after orthotopic transplantation insufficiently investigated findings are uncertain because analytical shortcomings. Also, most human studies have focused on individual members such as nitrate or asymmetric dimethylarginine (ADMA). In present article we report a pilot study investigating extensively before (OLT). By using fully validated, highly sensitive specific GC-MS GC-MS/MS methods nitrite, nitrate, ADMA its hydrolysis product dimethylamine (DMA), L-arginine L-ornithine were measured blood urine. Our gives strong evidence exceptional importance hepatic dimethylaminohydrolase (DDAH) activity for elimination systemic ADMA. end-stage disease synthesis NO well DDAH elevated. increase insufficient to efficiently eliminate overproduced transplanted graft capable clearing rapid sufficient manner. contrast from other groups, our shows that OLT living donor transplantation, second reported here, reperfusion does not cause drastic alterations with regard synthesis. concentration circulating fell temporally dramatically, while levels increased diametrically, likely due elevation arginase activity. relatively long-lasting decrease plasmatic seems affected reperfusion. suggests associated greatly elevated proteolytic hydrolytic enzymes including arginase. Suppression could be useful measure improve outcome remains further larger patient collectives. chemistry this area research also discussed article.