Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease.
Symmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine. Whereas the major route of asymmetric dimethylarginine elimination is the hydrolytic degradation by dimethylarginine dimethylaminohydrolase, SDMA is eliminated by renal excretion. SDMA does not directly inhibit NOS but is a competitor of arginine transport. This study showed for the first time that measurement of SDMA can be a marker of estimated GFR and extent of coronary artery disease (CAD). In 97 patients with CAD, SDMA was a marker of estimated GFR. On multiple regression analysis of the CAD parameter stenosis score, SDMA was the only parameter retained. In addition, endothelial cells from the third passage were cultured in medium that contained 70 micromol/L arginine and was incubated for 24 h in the presence of various concentration of SDMA (0, 2, 5, 10, and 100 micromol/L). The levels of nitrate and nitrite in conditioned media, the protein expression of NOS, and the content of reactive oxygen species in endothelial cells were determined. SDMA inhibited dose dependently the NO synthesis in intact endothelial cells, whereas it had no effect on protein expression of NOS. This effect was associated with an increase in reactive oxygen species. Co-incubation with L-arginine but not D-arginine reversed the effect of SDMA on NOS pathway. Our data suggest that SDMA reduced the endothelial NO synthesis, probably by limiting L-arginine supply to NOS. It is concluded that SDMA might be a useful parameter for detecting patients in very early stages of chronic kidney disease and for determining their risk for developing cardiovascular disease.
Institute of Clinical Pharmacology, University Hospital, Otto von Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. stefanie.bode-boeger@medizin.uni-magdeburg.de
Stefanie M
SM
Bode-Böger
Fortunato
F
Scalera
Jan T
JT
Kielstein
Jens
J
Martens-Lobenhoffer
Günter
G
Breithardt
Manfred
M
Fobker
Holger
H
Reinecke
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000378:metabolism; D007677:Kidney Function Tests / Q000379:methods*; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D012307:Risk Factors
D015415:Biomarkers; D004791:Enzyme Inhibitors; C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III