Nephrol Dial Transplant (2003) 18: 2542-2550
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia
1Department of Surgery, 2Department of Clinical Chemistry, 3Department of Internal Medicine and 4Department of Physiology, VU University Medical Center, Amsterdam and 5Department of Internal Medicine, Amphia Hospital (Langendijk), Breda, The Netherlands
Correspondence and offprint requests to: P. A. M. van Leeuwen, MD, PhD, VU University Medical Center, Department of Surgery, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Email: pam.vleeuwen{at}vumc.nl
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-
, 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.
Keywords: L-arginine; kidney; nitric oxide; nitric oxide synthase
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Baylis Sexual Dimorphism of the Aging Kidney: Role of Nitric Oxide Deficiency Physiology, June 1, 2008; 23(3): 142 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ellger, M. C. Richir, P. A. M. van Leeuwen, Y. Debaveye, L. Langouche, I. Vanhorebeek, T. Teerlink, and G. Van den Berghe Glycemic Control Modulates Arginine and Asymmetrical-Dimethylarginine Levels during Critical Illness by Preserving Dimethylarginine-Dimethylaminohydrolase Activity Endocrinology, June 1, 2008; 149(6): 3148 - 3157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Baylis Nitric oxide deficiency in chronic kidney disease Am J Physiol Renal Physiol, January 1, 2008; 294(1): F1 - F9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Palm, M. L. Onozato, Z. Luo, and C. S. Wilcox Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3227 - H3245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zoccali, R. Maas, S. Cutrupi, P. Pizzini, P. Finocchiaro, F. Cambareri, V. Panuccio, C. Martorano, F. Schulze, G. Enia, et al. Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections Nephrol. Dial. Transplant., March 1, 2007; 22(3): 801 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Carello, S. E. Whitesall, M. C. Lloyd, S. S. Billecke, and L. G. D'Alecy Asymmetrical dimethylarginine plasma clearance persists after acute total nephrectomy in rats Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H209 - H216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Teerlink ADMA metabolism and clearance Vascular Medicine, July 1, 2005; 10(1_suppl): S73 - S81. [Abstract] [PDF]
|
|
|
|
|
|
T. Teerlink ADMA metabolism and clearance Vascular Medicine, May 1, 2005; 10(2_suppl): S73 - S81. [Abstract] [PDF]
|
|
|
|
 |
|
 R. J. Nijveldt, M. P. C. Siroen, T. Teerlink, and P. A. M. van Leeuwen Elimination of Asymmetric Dimethylarginine by the Kidney and the Liver: A Link to the Development of Multiple Organ Failure? J. Nutr., October 1, 2004; 134(10): 2848S - 2852S. [Abstract] [Full Text] [PDF]
|
|