Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of nitric oxide. The concentration of both dimethylarginines is regulated by urina ry excretion, although ADMA, but not SDMA, is also subject ...Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of nitric oxide. The concentration of both dimethylarginines is regulated by urina ry excretion, although ADMA, but not SDMA, is also subject to degradation by dim ethylarginine dimethylaminohydrolase, which is highly expressed in the liver but also present in the kidney. The exact roles of the human liver and kidney in th e metabolism of dimethylarginines are currently unknown. Therefore, we aimed to investigate renal and hepatic handling of ADMA and SDMA in detail in 24 patients undergoing hepatic surgery. To calculate net organ fluxes and fractional extrac tion (FE) rates, blood was collected from an arterial line, the portal vein, hep atic vein, and renal vein, and blood flow of the hepatic artery, portal vein, an d renal vein was determined using Doppler ultrasound techniques. Results showed a significant net uptake (median [IQR]) of ADMA in both the liver (9.6 nmol/min [5.6- 13.2] ) and the kidney (12.1 nmol/min [1.3- 17.1]). SDMA uptake was pres ent not only in the kidney (12.7 nmol/min [3.5- 25.4]), but also in the liver ( 7.7 nmol/min [2.8- 16.4]). FE rates of ADMA for the liver and kidney were 5.0% (3.5% - 7.4% ) and 8.4% (1.3% - 13.9% ), respectively. For SDMA, hepat ic and renal FE rates were 3.4% (2.1% - 7.5% ) and 12.5% (3.6% - 16.2% ), respectively. In conclusion, this study gives a detailed description of the hepatic and renal elimination of dimethylarginines and shows that the clearing o f SDMA is not only confined to the kidney, but the human liver also takes up sub stantial amounts of SDMA from the portal and systemic circulation.展开更多
基金This work was supported by the National Nature and Sciences Grant (No. 30330300 andNo.30470806) and Committee of Provincial Science Study Foundation of Hunan (C2005-002)
文摘Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of nitric oxide. The concentration of both dimethylarginines is regulated by urina ry excretion, although ADMA, but not SDMA, is also subject to degradation by dim ethylarginine dimethylaminohydrolase, which is highly expressed in the liver but also present in the kidney. The exact roles of the human liver and kidney in th e metabolism of dimethylarginines are currently unknown. Therefore, we aimed to investigate renal and hepatic handling of ADMA and SDMA in detail in 24 patients undergoing hepatic surgery. To calculate net organ fluxes and fractional extrac tion (FE) rates, blood was collected from an arterial line, the portal vein, hep atic vein, and renal vein, and blood flow of the hepatic artery, portal vein, an d renal vein was determined using Doppler ultrasound techniques. Results showed a significant net uptake (median [IQR]) of ADMA in both the liver (9.6 nmol/min [5.6- 13.2] ) and the kidney (12.1 nmol/min [1.3- 17.1]). SDMA uptake was pres ent not only in the kidney (12.7 nmol/min [3.5- 25.4]), but also in the liver ( 7.7 nmol/min [2.8- 16.4]). FE rates of ADMA for the liver and kidney were 5.0% (3.5% - 7.4% ) and 8.4% (1.3% - 13.9% ), respectively. For SDMA, hepat ic and renal FE rates were 3.4% (2.1% - 7.5% ) and 12.5% (3.6% - 16.2% ), respectively. In conclusion, this study gives a detailed description of the hepatic and renal elimination of dimethylarginines and shows that the clearing o f SDMA is not only confined to the kidney, but the human liver also takes up sub stantial amounts of SDMA from the portal and systemic circulation.
