Cardiovascular tests: Use & limits of biochemical markers - Therapeutic measurements of ADMA involved in cardiovascular disorders

Current Pharmaceutical Design

Volumn 11, Issue 17, 2005, Pages 2177-2185

  Smith, Caroline L ^a   Vallance, Patrick ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; DIMETHYLARGININASE; INTERLEUKIN 1BETA; LIPOPOLYSACCHARIDE; METFORMIN; MYELIN BASIC PROTEIN; N(G) METHYLARGININE; N(G),N(G) DIMETHYLARGININE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PROTEIN ARGININE METHYLTRANSFERASE; RETINOIC ACID; ROSIGLITAZONE; TUMOR NECROSIS FACTOR ALPHA;

ALZHEIMER DISEASE; AMINO ACID ANALYSIS; AMINO ACID BLOOD LEVEL; AMINO ACID METABOLISM; AMINO ACID SYNTHESIS; AMINO ACID TRANSPORT; ANGIOGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC KIDNEY FAILURE; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LOCALIZATION; GENETIC VARIABILITY; HEMODIALYSIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYPERHOMOCYSTEINEMIA; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOPHYSIOLOGY; PREDICTION; PREECLAMPSIA; PRIORITY JOURNAL; PROTEIN FUNCTION; PULMONARY HYPERTENSION; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM;

ARGININE; BIOLOGICAL MARKERS; DIAGNOSTIC TECHNIQUES, CARDIOVASCULAR; HUMANS;

EID: 21044447271     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/1381612054367364     Document Type: Review

References (108)

1. Alheid U, Frolich JC, Forstermann U. Endothelium-derived relaxing factor from cultured human endothelial cells inhibits aggregation of human platelets. Thromb Res 1987; 47: 561-71.
2. Rees DD, Palmer RM, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 1989; 86: 3375-8.
3. Sakuma I, Stuehr DJ, Gross SS, Nathan C, Levi R. Identification of arginine as a precursor of endothelium-derived relaxing factor. Proc Natl Acad Sci USA 1988; 85: 8664-7.
4. Rees DD, Palmer RM, Hodson HF, Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelitim-dependent relaxation. Br J Pharmacol 1989; 96: 418-24.
5. Olken NM, Rusche KM, Richards MK, Marletta MA. Inactivation of macrophage nitric oxide synthase activity by NG-methyl-L-arginine. Biochem Biophys Res Commun 1991; 177: 828-33.
6. Frey C, Narayanan K, McMillan K, Spack L, Gross SS, Masters BS, et al. L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide synthases. J Biol Chem 1994; 269: 26083-91.
7. Pollock JS, Forstermann U, Mitchell JA, Warner TD, Schmidt HH, Nakane M, et al. Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. Proc Natl Acad Sci USA 1991; 88: 10480-4.
8. Griffith OW, Kilbourn RG. Nitric oxide synthase inhibitors: amino acids. Methods Enzymol 1996; 268: 375-92.
9. Pou S, Keaton L, Surichamorn W, Rosen GM. Mechanism of superoxide generation by neuronal nitric-oxide synthase. J Biol Chem 1999; 274: 9573-80.
10. Vasquez-Vivar J, Kalyanaraman B, Martasek P, Hogg N, Masters BS, Karoui H, et al. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 1998; 95: 9220-5.
11. Furchgott RF, Cherry PD, Zawadzki JV, Jothianandan D. Endothelial cells as mediators of vasodilation of arteries. J Cardiovasc Pharmacol 1984; 6 Suppl 2: S336-43.
12. Kakimoto Y, Akazawa S. Isolation and identification of N-G, N-G- and N-G, N′-G-dimethyl-arginine, N-epsilon-mono-, di-, and trimethyllysine, and glucosylgalactosyl- and galactosyl-delta-hydroxylysine from human urine. J Biol Chem 1970; 245: 5751-8.
13. Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572-5.
14. Vallance P, Leone A, Calver A, Collier J, Moncada S. Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. J Cardiovasc Pharmacol 1992; 20 Suppl 12: S60-2.
15. MacAllister RJ, Fickling SA, Whitley GS, Vallance P. Metabolism of methylarginines by human vasculature; implications for the regulation of nitric oxide synthesis. Br J Pharmacol 1994; 112: 43-8.
16. Deibler GE, Martenson RE. Chromatographic fractionation of myelin basic protein. Partial characterization and methylarginine contents of the multiple forms. J Biol Chem 1973; 248: 2392-6.
17. Morse RK, Vergnes JP, Malloy J, McManus IR. Sites of biological methylation of proteins in cultured chick muscle cells. Biochemistry 1975; 14: 4316-25.
18. Miyake M, Kakimoto Y. Synthesis and degradation of methylated proteins of mouse organs: correlation with protein synthesis and degradation. Metabolism 1976; 25: 885-96.
19. Small DH, Carnegie PR. In vivo methylation of an arginine in chicken myelin basic protein. J Neurochem 1982; 38: 184-90.
20. Boisvert FM, Cote J, Boulanger MC, Richard S. Proteomic Analysis of Arginine-methylated Protein Complexes. Mol Cell Proteomics 2003; 2: 1319-30.
21. Casellas P, Jeanteur P. Protein methylation in animal cells. II. Inhibition of S-adenosyl-L-methionine: protein(arginine) N-methyltransferase by analogs of S-adenosyl-L-homocysteine. Biochim Biophys Acta 1978; 519: 255-68.
22. Tang J, Frankel A, Cook RJ, Kim S, Paik WK, Williams KR, et al. PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells. J Biol Chem 2000; 275: 7723-30.
23. Tang J, Gary JD, Clarke S, Herschman HR. PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation. J Biol Chem 1998; 273: 16935-45.
24. Rawal N, Rajpurohit R, Lischwe MA, Williams KR, Paik WK, Kim S. Structural specificity of substrate for S-adenosylmethionine: protein arginine N-methyltransferases. Biochim Biophys Acta 1995; 1248: 11-8.
25. Boisvert FM, Cote J, Boulanger MC, Cleroux P, Bachand F, Autexier C, et al. Symmetrical dimethylarginine methylation is required for the localization of SMN in Cajal bodies and pre-mRNA splicing. J Cell Biol 2002; 159: 957-69.
26. Frankel A, Clarke S. PRMT3 is a distinct member of the protein arginine N-methyltransferase family. Conferral of substrate specificity by a zinc-finger domain. J Biol Chem 2000; 275: 32974-82.
27. Boger RH, Bode-Boger SM, Sydow K, Heistad DD, Lentz SR. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol 2000; 20: 1557-64.
28. Osanai T, Saitoh M, Sasaki S, Tomita H, Matsunaga T, Okumura K. Effect of shear stress on asymmetric dimethylarginine release from vascular endothelial cells. Hypertension 2003; 42: 985-90.
29. Lee JH, Cook JR, Yang ZH, Mirochnitchenko O, Gunderson S, Felix AM, et al. PRMT7: A new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J Biol Chem 2004; Oct 19: [Epub ahead of print].
30. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999; 399: 601-5.
31. Frankel A, Yadav N, Lee J, Branscombe TL, Clarke S, Bedford MT. The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity. J Biol Chem 2002; 277: 3537-43.
32. Chen D, Ma H, Hong H, Koh SS, Huang SM, Schurter BT, et al. Regulation of transcription by a protein methyltransferase. Science 1999; 284: 2174-7.
33. Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu YJ. Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha. J Biol Chem 2002; 277: 28624-30.
34. Rho J, Choi S, Seong YR, Cho WK, Kim SH, Im DS. Prmt5, which forms distinct homo-oligomers, is a member of the protein-arginine methyltransferase family. J Biol Chem 2001; 276: 11393-401.
35. McDermott JR. Studies on the catabolism of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine in the rabbit. Biochem J 1976; 154: 179-84.
36. Ogawa T, Kimoto M, Sasaoka K. Purification and properties of a new enzyme, NG, NG-dimethylarginine dimethylaminohydrolase, from rat kidney. J Biol Chem 1989; 264: 10205-9.
37. Ogawa T, Kimoto M, Sasaoka K. Occurrence of a new enzyme catalyzing the direct conversion of NG, NG-dimethyl-L-arginine to L-citrulline in rats. Biochem Biophys Res Commun 1987; 148: 671-7.
38. Kimoto M, Whitley GS, Tsikii H, Ogawa T. Detection of NG, NG-dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody. J Biochem (Tokyo) 1995; 117: 237-8.
39. MacAllister RJ, Parry H, Kimoto M, Ogawa T, Russell RJ, Hodson H, et al. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996; 119: 1533-40.
40. Leiper JM, Santa Maria J, Chubb A, MacAllister RJ, Charles IG, Whitley GS, et al. Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 1999; 343: 209-14.
41. Tran CT, Fox MF, Vallance P, Leiper JM. Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics 2000; 68: 101-5.
42. Birdsey GM, Leiper JM, Valiance P. Intracellular localization of dimethylarginine dimethylaminohydrolase overexpressed in an endothelial cell line. Acta Physiol Scand 2000; 168: 73-9.
43. Leiper J, Murray-Rust J, McDonald N, Vallance P. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci USA 2002; 99: 13527-32.
44. Murray-Rust J, Leiper J, McAlister M, Phelan J, Tilley S, Santa Maria J, et al. Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. Nat Struct Biol 2001; 8: 679-83.
45. Knipp M, Braun O, Gehrig PM, Sack R, Vasak M. Zn(II)-free dimethylargininase-1 (DDAH-1) is inhibited upon specific Cys-S-nitrosylation. J Biol Chem 2003; 278: 3410-6.
46. Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 2003; 23: 1455-9.
47. Achan V, Tran CT, Arrigoni F, Whitley GS, Leiper JM, Vallance P. all-trans-Retinoic acid increases nitric oxide synthesis by endothelial cells: a role for the induction of dimethylarginine dimethylammohydrolase. Circ Res 2002; 90: 764-9.
48. Holden DP, Cartwright JE, Nussey SS, Whitley GS. Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine. Circulation 2003; 108: 1575-80.
49. Teerlink T, Neele SJ, de Jong S, Netelenbos JC, Stehouwer CD. Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women. Clin Sci (Lond) 2003; 105: 67-71.
50. Ueda S, Kato S, Matsuoka H, Kimoto M, Okuda S, Morimatsu M, et al. Regulation of cytokine-induced nitric oxide synthesis by asymmetric dimethylarginine: role of dimethylarginine dimethylaminohydrolase. Circ Res 2003; 92: 226-33.
51. Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999; 99: 3092-5.
52. Laussmann T, Janosi RA, Fingas CD, Schlieper GR, Schlack W, Schrader J, et al. Myocardial proteome analysis reveals reduced NOS inhibition and enhanced glycolytic capacity in areas of low local blood flow. FASEB J 2002; 16: 628-30.
53. Jones LC, Tran CT, Leiper JM, Hingorani AD, Vallance P. Common genetic variation in a basal promoter element alters DDAH2 expression in endothelial cells. Biochem Biophys Res Commun 2003; 310: 836-43.
54. Valkonen V-P. A novel mutation in Dimethylarginine dimethylaminohydrolase (DDAH 1) gene: A genetic risk factor for cardiovascular disorders in Finnish men. American Heart Association 2003 meeting Abstract #12.
55. Jang JJ, Ho HK, Kwan HH, Fajardo LF, Cooke JP. Angiogenesis is impaired by hypercholesterolemia: role of asymmetric dimethylarginine. Circulation 2000; 102: 1414-9.
56. Smith CL, Birdsey GM, Anthony S, Arrigoni FI, Leiper JM, Vallance P. Dimethylarginine Dimethylaminohydrolase activity modulates ADMA Levels, VEGF Expression And Cell Phenotype. Biochem Biophys Res Communications 2003; 308: 984-989.
57. Kostourou V, Robinson SP, Cartwright JE, Whitley GS. Dimethylarginine dimethylaminohydrolase I enhances tumour growth and angiogenesis. Br J Cancer 2002; 87: 673-80.
58. Hecker M, Sessa WC, Harris HJ, Anggard EE, Vane JR. 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: 8612-6.
59. Tsikas D, Boger RH, Sandmann J, Bode-Boger SM, Frolich JC. Endogenous nitric oxide synthase inhibitors are responsible for the L-arginine paradox. FEBS Lett 2000; 478: 1-3.
60. Schmidt K, Klatt P, Mayer B. Characterization of endothelial cell amino acid transport systems involved in the actions of nitric oxide synthase inhibitors. Mol Pharmacol 1993; 44: 615-21.
61. Bogle RG, Moncada S, Pearson JD, Mann GE. Identification of inhibitors of nitric oxide synthase that do not interact with the endothelial cell L-arginine transporter. Br J Pharmacol 1992; 105: 768-70.
62. Xiao S, Wagner L, Mahaney J, Baylis C. Uremic levels of urea inhibit L-arginine transport in cultured endothelial cells. Am J Physiol Renal Physiol 2001; 280: F989-95.
63. Bogle RG, MacAllister RJ, Whitley GS, Vallance P. Induction of NG-monomethyl-L-arginine uptake: a mechanism for differential inhibition of NO synthases? Am J Physiol 1995; 269: C750-6.
64. Cardounel AJ, Zweier JL. Endogenous methylarginines regulate neuronal nitric-oxide synthase and prevent excitotoxic injury. J Biol Chem 2002; 277: 33995-4002.
65. Fickling SA, Holden DP, Cartwright JE, Nussey SS, Vallance P, Whitley GS. Regulation of macrophage nitric oxide synthesis by endothelial cells: a role for NG, NG-dimethylarginine. Acta Physiol Scand 1999; 167: 145-50.
66. Hattori Y, Kasai K, Gross SS. Cationic amino acid transporter gene expression in cultured vascular smooth muscle cells and in rats. Am J Physiol 1999; 276: H2020-8.
67. Wileman SM, Mann GE, Baydoun AR. Induction of L-arginine transport and nitric oxide synthase in vascular smooth muscle cells: synergistic actions of pro-inflammatory cytokines and bacterial lipopolysaccharide. Br J Pharmacol 1995; 116: 3243-50.
68. Patel JM, Abeles AJ, Block ER. Nitric oxide exposure and sulfhydryl modulation alter L-arginine transport in cultured pulmonary artery endothelial cells. Free Radic Biol Med 1996; 20: 629-37.
69. Baydoun AR, Emery PW, Pearson JD, Mann GE. Substrate-dependent regulation of intracellular amino acid concentrations in cultured bovine aortic endothelial cells. Biochem Biophys Res Commun 1990; 173: 940-8.
70. Zharikov SI, Block ER. Characterization of L-arginine uptake by plasma membrane vesicles isolated from cultured pulmonary artery endothelial cells. Biochim Biophys Acta 1998; 1369: 173-83.
71. Paik WK, Kim S. Omega-N-methylarginine in protein. J Biol Chem 1970; 245: 88-92.
72. Teerlink T, Nijveldt RJ, de Jong S, van Leeuwen PA. Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem 2002; 303: 131-7.
73. MacAllister RJ, Rambausek MH, Vallance P, Williams D, Hoffmann KH, Ritz E. Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure. Nephrol Dial Transplant 1996; 11: 2449-52.
74. Zoccali C, Bode-Boger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 2001; 358: 2113-7.
75. Abe T, Tohgi H, Murata T, Isobe C, Sato C. Reduction in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in the cerebrospinal fluid during aging and in patients with Alzheimer's disease, Neurosci Lett 2001; 312: 177-9.
76. Mulder C, Wahlund LO, Blomberg M, de Jong S, van Kamp GJ, Scheltens P, et al. Alzheimer's disease is not associated with altered concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine in cerebrospinal fluid. J Neural Transm 2002; 109: 1203-8.
77. Vishwanathan K, Tackett RL, Stewart JT, Bartlett MG. Determination of arginine and methylated arginines in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 2000; 748: 157-66.
78. Tsikas D, Schubert B, Gutzki FM, Sandmann J, Frolich JC. Quantitative determination of circulating and urinary asymmetric dimethylarginine (ADMA) in humans by gas chromatography-tandem mass spectrometry as methyl ester tri(N-pentafluoropropionyl) derivative. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 798: 87-99.
79. Martens-Lobenhoffer J, Bode-Boger SM. Simultaneous detection of arginine, asymmetric dimethylarginine, symmetric dimethylarginine and citrulline in human plasma and urine applying liquid chromatography-mass spectrometry with very straightforward sample preparation. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 798: 231-9.
80. Knipp M, Vasak M. A colorimetric 96-well microtiter plate assay for the determination of enzymatically formed citrulline. Anal Biochem 2000; 286: 257-64.
81. Lou MF. Human muscular dystrophy: elevation of urinary dimethylarginines. Science 1979; 203: 668-70.
82. Carnegie PR, Fellows FC, Symington GR. Urinary excretion of methylarginine in human disease. Metabolism 1977; 26: 531-7.
83. Valkonen VP, Paiva H, Salonen JT, Lakka TA, Lehtimaki T, Laakso J, et al. Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 2001; 358: 2127-8.
84. Osanai T, Fujiwara N, Saitoh M, Sasaki S, Tomita H, Nakamura M, et al. Relationship between salt intake, nitric oxide and asymmetric dimethylarginine and its relevance to patients with endstage renal disease. Blood Purif 2002; 20: 466-8.
85. Zoccali C, Mallamaci F, Maas R, Benedetto FA, Tripepi G, Malatino LS, et al. CREED Investigators. Left ventricular hypertrophy, cardiac remodeling and asymmetric dimethylarginine (ADMA) in hemodialysis patients. Kidney Int 2002; 62: 339-45.
86. Matsuoka H, Itoh S, Kimoto M, Kohno K, Tamai O, Wada Y, et al. Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension. Hypertension 1997; 29: 242-7.
87. Cross JM, Donald A, Vallance PJ, Deanfield JE, Woolfson RG, MacAllister RJ. Dialysis improves endothelial function in humans. Nephrol Dial Transplant 2001; 16: 1823-9.
88. Hand MF, Haynes WG, Webb DJ. Hemodialysis and L-arginine, but not D-arginine, correct renal failure-associated endothelial dysfunction. Kidney Int 1998; 53: 1068-77.
89. Cross JM, Donald AE, Kharbanda R, Deanfield JE, Woolfson RG, MacAllister RJ. Acute administration of L-arginine does not improve arterial endothelial function in chronic renal failure. Kidney Int 2001; 60: 2318-23.
90. Arrigoni FI, Vallance P, Haworth SG, Leiper JM. Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation 2003; 107: 1195-201.
91. Gorenflo M, Zheng C, Werle E, Fiehn W, Ulmer HE. Plasma levels of asymmetrical dimethyl-L-arginine in patients with congenital heart disease and pulmonary hypertension. J Cardiovasc Pharmacol 2001; 37: 489-92.
92. Millatt LJ, Whitley GS, Li D, Leiper JM, Siragy HM, Carey RM, et al. Evidence for dysregulation of dimethylarginine dimethylaminohydrolase I in chronic hypoxia-induced pulmonary hypertension. Circulation 2003; 108: 1493-8.
93. Fickling SA, Williams D, Vallance P, Nussey SS, Whitley GS. Plasma concentrations of endogenous inhibitor of nitric oxide synthesis in normal pregnancy and pre-eclampsia. Lancet 1993; 342: 242-3.
94. Holden DP, Fickling SA, Whitley GS, Nussey SS. Plasma concentrations of asymmetric dimethylarginine, a natural inhibitor of nitric oxide synthase, in normal pregnancy and preeclampsia. Am J Obstet Gynecol 1998; 178: 551-6.
95. Savvidou MD, Hingorani AD, Tsikas D, Frolich JC, Vallance P, Nicolaides KH. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 2003; 361: 1511-7.
96. Boger RH, Lentz SR, Bode-Boger SM, Knapp HR, Haynes WG. Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans. Clin Sci (Lond) 2001; 100: 161-7.
97. Stuhlinger MC, Oka RK, Graf EE, Schmolzer I, Upson BM, Kapoor O, et al. Endotheiial dysfunction induced by hyperhomocyst(e)inemia: role of asymmetric dimethylarginine. Circulation 2003; 108: 933-8.
98. Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, et al. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999; 99: 1141-1146.
99. Stuhlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation 2001; 104: 2569-75.
100. Paiva H, Lehtimaki T, Laakso J, Ruokonen I, Rantalaiho V, Wirta O, et al. 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. Metabolism 2003; 52: 303-7.
101. Stuhlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 2002; 287: 1420-6.
102. Asagami T, Abbasi F, Stuelinger M, Lamendola C, McLaughlin T, Cooke JP, et al. Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. Metabolism 2002; 51: 843-6.
103. Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002; 106: 987-92.
104. Nakagomi S, Kiryu-Seo S, Kimoto M, Emson PC, Kiyama H. Dimethylarginine dimethylaminohydrolase (DDAH) as a nerve-injury-associated molecule: mRNA localization in the rat brain and its coincident up-regulation with neuronal NO synthase (nNOS) in axotomized motoneurons. Eur J Neurosci 1999; 11: 2160-6.
105. Schulze F, Wesemann R, Schwedhelm E, Sydow K, Albsmeier J, Cooke JP, et al. Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay. Clin Chem Lab Med 2004; 42: 1377-83.
106. Domenico R. Pharmacology of nitric oxide: molecular mechanisms and therapeutic strategies. Curr Pharm Design 2004; 10(14): 1667-76.
107. Morbidelli L, Donnini S, Ziche M. Role of nitric oxide in the modulation of angiogenesis. Curr Pharm Design 2003; 9(7): 521-30.
108. Tiboni GM, Clementini E. Teratological consequences of nitric oxide synthesis inhibition. Curr Pharm Design 2004; 10(22): 2759-67.