Metabolism - Clinical and Experimental
Volume 52, Issue 3 , Pages 303-307 , March 2003

Plasma concentrations of asymmetric-dimethyl-arginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy

Received 3 April 2002 ,Accepted 26 September 2002.

References 

  1. Hecker M, Sessa WC, Harris HJ, et al.  The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: Cultured endothelial cells recycle L-citrulline to L-arginine. Proc Natl Acad Sci USA. 1990;87:8612–8616
  2. Ito A, Tsao PS, Adimoolam S, et al.  Novel mechanism for endothelial dysfunction: Dysregulation of dimethylarginine dimethylaminohydrolase. Circulation. 1999;99:3092–3095
  3. Böger RH, Bode-Böger SM, Szuba A, et al.  Asymmetric dimethylarginine (ADMA): A novel risk factor for endothelial dysfunction: Its role in hypercholesterolemia. Circulation. 1998;98:1842–1847
  4. Miyazaki H, Matsuoka H, Cooke JP, et al.  Endogenous nitric oxide synthase inhibitor, a novel marker of atherosclerosis. Circulation. 1999;99:1141–1146
  5. Surdacki A, Nowicki M, Sandmann J, et al.  Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol. 1999;33:652–658
  6. Goonasekera CD, Shah V, Rees DD, et al.  Vascular endothelial cell activation associated with increased plasma asymmetric dimethyl arginine in children and young adults with hypertension: A basis for atheroma?. Blood Press. 2000;9:16–21
  7. Valkonen VP, Päivä H, Salonen JT, et al.  Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet. 2001;358:2127–2128
  8. De Vriese AS, Verbeuren TJ, Van de Voorde J, et al.  Endothelial dysfunction in diabetes. Br J Pharmacol. 2000;130:963–974
  9. Cosentino F, Luscher TF. Endothelial dysfunction in diabetes mellitus. J Cardiovasc Pharmacol. 1998;32(suppl 3):54–61
  10. Pyörälä K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: An epidemiologic view. Diabetes Metab Rev. 1987;3:463–524
  11. Haffner SM, Lehto S, Rönnemaa T, et al.  Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234
  12. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–376
  13. Hattenbach LO, Allers A, Klais C, et al.  L-arginine-nitric oxide pathway-related metabolites in the aqueous humor of diabetic patients. Invest Ophthalmol Vis Sci. 2000;41:213–217
  14. Laufs U, La Fata V, Plutzky J, et al.  Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–1135
  15. Xiong Y, Lu R, Li YJ, et al.  Elevation of an endogenous inhibitor of nitric oxide synthase in diabetic rat serum. Zhongguo Yao Li Xue Bao. 1997;18:511–514
  16. Masuda H, Goto M, Tamaoki S, et al.  Accelerated intimal hyperplasia and increased endogenous inhibitors for NO synthesis in rabbits with alloxan-induced hyperglycaemia. Br J Pharmacol. 1999;126:211–218
  17. Abbasi F, Asagmi T, Cooke JP, et al.  Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus. Am J Cardiol. 2001;88:1201–1203
  18. Wirta O, Pasternack A, Laippala P, et al.  Glomerular filtration rate and kidney size after six years disease duration in non-insulin-dependent diabetic subjects. Clin Nephrol. 1996;45:10–17
  19. Chiarelli F, Cipollone F, Romano F, et al.  Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: Relation to glomerular hyperfiltration. Diabetes. 2000;49:1258–1263
  20. Chaiken RL, Eckert-Norton M, Bard M, et al.  Hyperfiltration in African-American patients with type 2 diabetes. Cross-sectional and longitudinal data. Diabetes Care. 1998;21:2129–2134
  21. Jeppsson JO, Jerntorp P, Sundkvist G, et al.  Measurement of hemoglobin A1c by a new liquid-chromatographic assay: Methodology, clinical utility, and relation to glucose tolerance evaluated. Clin Chem. 1986;32:1867–1872
  22. Causse E, Siri N, Arnal JF, et al.  Determinations of asymmetrical dimethylarginine by capillary electrophoresis-laser-induced fluorescence. J Chromatogr B Biomed Sci Appl. 2000;741:77–83
  23. Pi J, Kumagai Y, Sun G, et al.  Improved method for simultaneous determination of L-arginine and its mono- and dimethylated metabolites in biological samples by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 2000;742:199–203
  24. Vishwanathan K, Tackett RL, Stewart JT, et al.  Determination of arginine and methylated arginines in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 2000;748:157–166
  25. Cosentino F, Hishikawa K, Katusic ZS, et al.  High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation. 1997;96:25–28
  26. Graier WF, Wascher TC, Lackner L, et al.  Exposure to elevated D-glucose concentrations modulates vascular endothelial cell vasodilatory response. Diabetes. 1993;42:1497–1505
  27. Cooper ME. Pathogenesis, prevention and treatment of diabetic nephropathy. Lancet. 1998;352:213–219
  28. Craven PA, DeRubertis FR, Melhem M. Nitric oxide in diabetic nephropathy. Kidney Int Suppl. 1997;60:S46–S53
  29. Mattar AL, Fujihara CK, Ribeiro MO, et al.  Renal effects of acute and chronic nitric oxide inhibition in experimental diabetes. Nephron. 1996;74:136–143
  30. Schoonmaker GC, Fallet RW, Carmines PK. Superoxide anion curbs nitric oxide modulation of afferent arteriolar ANG II responsiveness in diabetes mellitus. Am J Physiol Renal Physiol. 2000;278:F302–F309
  31. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32(suppl 2):64–78
  32. Vallance P, Leone A, Calver A, et al.  Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet. 1992;339:572–575
  33. Kielstein JT, Böger RH, Bode-Böger SM, et al.  Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol. 2002;13:170–176
  34. Wirta V, Saransaari P, Wirta O, et al.  Methylenetetrahydrofolate reductase gene polymorphism, hyperhomocysteinaemia and occlusive retinal vascular disease in type 2 diabetic and nondiabetic subjects. Clin Nephrol. 2002;58:171–178
  35. Soper CP, Barron JL, Hyer SL. Long-term glycaemic control directly correlates with glomerular filtration rate in early type 1 diabetes mellitus before the onset of microalbuminuria. Diabet Med. 1998;15:1010–1014
  36. Holden DP, Fickling SA, Whitley GS, et al.  Plasma concentrations of asymmetric dimethylarginine, a natural inhibitor of nitric oxide synthase, in normal pregnancy and preeclampsia. Am J Obstet Gynecol. 1998;178:551–556
  37. Cardinale CP, Fard A, Eisenberg MS, et al.  Elevated plasma level of asymmetric dimethylarginine (ADMA) is associated with atherosclerotic disease of the thoracic aorta. J Am Coll Cardiol. 2001;37:648A; (suppl A, abstr)
  38. Päivä H, Laakso J, Laine H, et al.  Plasma asymmetric dimethylarginine and hyperemic myocardial blood flow in young subjects with borderline hypertension or familial hypercholesterolemia. J Am Coll Cardiol. 2002;40:1241–1247

 Supported by grants from the Elli and Elvi Oksanen Fund of the Pirkanmaa Fund under the auspices of Finnish Cultural Foundation, the Juho Vainio Foundation, and the Medical Research Fund of the Tampere University Hospital.

☆☆ Address reprint requests to Hannu Päivä, MD, Tampere University Hospital, Department of Internal Medicine, PO Box 2000, FIN-33521, Tampere, Finland.

PII: S0026-0495(02)05264-2

doi: 10.1053/meta.2003.50048

Metabolism - Clinical and Experimental
Volume 52, Issue 3 , Pages 303-307 , March 2003