The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA)

Abstract

Background and Aims: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. Although both dimethylarginines may be important regulators of the arginine–NO pathway, their metabolism is largely unknown. Both dimethylarginines are removed from the body by urinary excretion. However, ADMA is also subject to enzymatic degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which is highly expressed in the liver. To elucidate the role of the liver in the metabolism of ADMA, we aimed to investigate dimethylarginine handling of the liver in detail. Methods: Ten male Wistar rats were used for this study. Blood flow was measured using radiolabeled microspheres according to the reference sample method. Concentrations of dimethylarginines were measured by HPLC. The com-bination of arteriovenous concentration difference and organ blood flow allowed calculation of net organ fluxes and fractional extraction rates. Results:Both the liver (0.89±0.11) and the kidney (0.68±0.06) showed a high net uptake (nmol/100 g body weight (BW)/min) of ADMA, whereas a significant net uptake of SDMA was only observed in the kidney (0.34±0.04). For the liver, fractional extraction rates were 29.5% ±3.0 for ADMA and 0.0%±3.7 for SDMA. Fractional extraction rates of ADMA and SDMA for the kidney were 36.0%±2.7 and 31.6%±3.8, respectively. Conclusions:The liver plays an important role in the metabolism of ADMA by taking up large amounts of ADMA from the systemic circulation.