Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia.
BACKGROUND
Asymmetrical dimethylarginine (ADMA) is capable of inhibiting nitric oxide synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. The potential role of inflammation in the metabolism of ADMA has been elucidated in an in vitro model using tumour necrosis factor-alpha, resulting in a decreased activity of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH). The kidney probably plays a crucial role in the metabolism of ADMA by both urinary excretion and degradation by DDAH. We aimed to further elucidate the role of the kidney in a rat model under basal conditions and during endotoxaemia.


METHODS
Twenty-five male Wistar rats weighing 275-300 g were used for this study. The combination of arteriovenous concentration differences and kidney blood flow allowed calculation of net organ fluxes. Blood flow was measured using radiolabelled microspheres according to the reference sample method. Concentrations of ADMA, SDMA and arginine were measured by high-performance liquid chromatography.


RESULTS
The kidney showed net uptake of both ADMA and SDMA and fractional extraction rates were 35% and 31%, respectively. Endotoxaemia resulted in a lower systemic ADMA concentration (P = 0.01), which was not explained by an increased net renal uptake. Systemic SDMA concentrations increased during endotoxaemia (P = 0.007), which was accompanied by increased creatinine concentrations.


CONCLUSIONS
The rat kidney plays a crucial role in the regulation of concentrations of dimethylarginines, as both ADMA and SDMA were eliminated from the systemic circulation in substantial amounts. Furthermore, evidence for the role of endotoxaemia in the metabolism of dimethylarginines was obtained as plasma levels of ADMA were significantly lower in endotoxaemic rats.
Nijveldt
Robert J
RJ
Department of Surgery, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
Teerlink
Tom
T
van Guldener
Coen
C
Prins
Hubert A
HA
van Lambalgen
Antonie A
AA
Stehouwer
Coen D A
CD
Rauwerda
Jan A
JA
van Leeuwen
Paul A M
PA
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D019446:Endotoxemia / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D004791:Enzyme Inhibitors; D007668:Kidney / Q000502:physiology* / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D008863:Microspheres; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase