Blood methylarginines and disturbed regulation of nitric oxide bioavailability in patients of hemodialysis
Abstract
Studies of the role of methylarginines (MA) in the regulation of nitric oxide (NO) bioavailability showed that monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA) competitively inhibit NO-synthase (NOS). Symmetric dimethylarginine (SDMA) is not active in respect of NOS. It however regulates transmembrane transport of L-arginine – a NOS substrate. High MA concentration in blood MA was shown to depresses many vascular functions which depend on NO. High level of MA contributes to the development of atherosclerosis and hypertension. Blood concentrations of MA, serotonin (5-HT), its metabolite (5-HIAA) and catecholamines were measured using HPLC with electrochemical and fluorometric detectors in healthy individuals and hemodialysis patients. The levels of ADMA, MMA and SDMA were significantly higher in hemodialysis than in control group. Hemodialysis reduced these levels, but not completely restored their normal values. Level of 5-HT in platelet-poor plasma was 6 times higher, and 5-HIAA was almost 30 times higher in hemodialysis patients than in the control group. Dialysis had no effect on plasma arginine and platelet 5-HT. Significant correlations were found between monoamines and methylarginines in hemodialysis patients, but not in the control group. Our data suggest that vascular pathology in hemodialysis patients could not be attributed to any systems studied. One should keep in mind their interaction and mutual substitution. Our and literature data allow one to assume that negative correlation between arginine and norepinephrine reflects the peculiarities of reaction to the medication stress which are characteristic for hypertensive patients. This work was supported by RFBR grant 08-04-00951.
About the Authors
M. A. Gilinsky
Institute of Physiology, Siberian branch of RAS, Novosibirsk
Russian Federation
Russian Federation
S. I. Anokhin
Siberian Regional Medical Center, Novosibirsk
Russian Federation
Russian Federation
S. A. Koroleva
Siberian Regional Medical Center, Novosibirsk
Russian Federation
Russian Federation
T. V. Latysheva
Institute of Physiology, Siberian branch of RAS, Novosibirsk
Russian Federation
Russian Federation
G. M. Petrakova
Institute of Physiology, Siberian branch of RAS, Novosibirsk
Russian Federation
Russian Federation
R. A. Suhovershin
Institute of Physiology, Siberian branch of RAS, Novosibirsk
Russian Federation
Russian Federation
References
1. Гилинский М.А., Латышева Т.В., Семенова Л.П. Определение катехоламинов, серотонина и 5-гидроксииндолуксусной кислоты в одной пробе крови // Клин. лаб. диагностика. 2007. № 6. C. 25–28.
2. Гилинский М.А. Асимметричный диметиларгинин: метаболизм, аргининовый парадокс, патофизиология // Успехи физиол. наук. 2007. Т. 38. № 3. С. 21–39.
3. Гилинский М.А., Анохин С.И., Зеунова Н.А. и др. Моноамины крови при хронической почечной недостаточности: эффект гемодиализа // Нефрология и диализ. 2009. Т. 11. № 4. С. 310–313.
4. Сидельников Ю.Н., Сиворакша Г.А. Концентрация серотонина в крови больных геморрагической лихорадкой с почечным синдромом // Клин. лаб. диагностика. 1996. № 5. С. 21–22.
5. Федорченко Ю.Л., Давидович И.М. Динамика общего, свободного и тромбоцитарного серотонина в плазме крови больных геморрагической лихорадкой с почечным синдромом // Клиническая медицина. 1990. Т. 68. № 6. С. 62–64.
6. Al Banchaabouchi M., Marescau B., Possemiers I. et al. NG, NG-Dimethylarginine and NG, N’G-dimethylarginine in renal insufficiency // Pflugers Arch–Eur. J. Physiol. 2000. Vol. 439. № 5. P. 524–531.
7. Barisić I., Pivac N., Mück-Seler D. et al. Comorbid depression and platelet serotonin in hemodialysis patients // Nephr. Clin. Pract. 2004. Vol. 96. № 1. P. 10–14.
8. Böger R.H., Endres H.G., Schwedhelm E. et al. Asymmetric dimethylarginine as an independent risk marker for mortality in ambulatory patients with peripheral arterial disease // J. Intern. Med. 2011. Vol. 269. № 3. P. 349–361.
9. Böger R.H., Schwedhelm E., Maas R. et al. ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study // Vasc. Med. 2005. Vol. 10. Suppl 1. P. S97–S102.
10. Boger R.H., Zoccali C. ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease // Atheroscler. Suppl. 2003. Vol. 4. № 4. P. 23–28.
11. Brewster U.C., Ciampi M.A., Abu-Alfa A.K. et al. Addition of sertraline to other therapies to reduce dialysis-associated hypotension // Nephrology (Carlton), 2003. Vol. 8 (6). P. 296–301.
12. Borgdorff P., Fekkes D., Tangelder G.J. Hypotension caused by extracorporeal circulation: serotonin from pump-activated platelets triggers nitric oxide release // Circulation, 2002. Vol. 106, № 20. P. 2588–2593.
13. Brunini T.M., Roberts N.B., Yaqoob M.M. et al. Activation of l-arginine transport in undialysed chronic renal failure and continuous ambulatory peritoneal dialysis patients // Clin. Exp. Pharmacol. Physiol. 2006. Vol. 33. P. 114–118.
14. Cooke J.P. Asymmetrical dimethylarginine the uber marker? // Circulation. 2004. Vol. 109. P. 1813–1819.
15. de Jong S., Teerlink T. Analysis of asymmetric dimethylarginine in plasma using a monolithic column // Analyt. Biochem. 2006. Vol. 353. P. 287–289.
16. Fleck C., Schweitzer F., Karge E. et al. Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases // Clin. Chim. Acta. 2003. Vol. 336. № (1–2). P. 1–12.
17. Kielstein J.T., Böger R.H., Bode-Böger S.M. et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease // J. Am. Soc. Nephrol. 1999. Vol. 10. № 3. P. 594–600.
18. Kielstein J.T., Simmel S., Bode-Boger S.M. et al. Subpressor dose asymmetric dimethylarginine modulates renal function in humans through nitric oxide synthase inhibition // Kidney Blood Press. Res. 2004. Vol. 27. P. 143–147.
19. Kielstein J.T., Zoccali C. Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin coming of age? // Am. J. Kidney Dis. 2005. Vol. 46. P. 186–202.
20. Kimmel P.L., Cukor D., Cohen S.D. et al. Depression in end-stage renal disease patients: a critical review // Adv. Chronic Kidney Dis., 2007. Vol. 14. № 4. P. 328–334.
21. Lechin F., van der Dijs B., Lechin A.E. Circulating serotonin, catecholamines, and central nervous system circuitry related to some cardiorespiratory, vascular, and hematological disorders // J. of Appl. Res. 2005. Vol. 5. No. 4. P. 605–621.
22. Lindner A., Charra B., Sherrard D.J. et al. Accelerated atherosclerosis in prolonged maintenance hemodialysis // N. Engl. J. Med. 1974. Vol. 290. P. 697–701.
23. MacAllister R.J., Rambausek M.H., Vallance P. et al. Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure // Nephrol. Dial. Transplant. 1996. Vol. 11. P. 2449–2452.
24. Mendes Ribeiro A.C., Roberts N.B., Lane C. et al. Accumulation of the endogenous l-arginine analogue NG-monomethyl-larginine in end stage renal failure patients on regular haemodialysis // Exp. Physiol. 1996. Vol. 81. P. 475–481.
25. Picard M., Olichon D., Gombert J. Determination of serotonin in plasma by liquid chromatography with electrochemical detection // J. Chromatogr. 1985. Vol. 341. P. 445–451.
26. Prados P., Matsunaga H., Mori T. et al. Сhanges of plasma L-arginine levels in spontaneously hypertensive rats under induced hypotension // Biomed. Chromatogr. 1999. Vol. 13. P. 27–32.
27. Ravani P., Tripepi G., Malberti F. et al. Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach // J. Am. Soc. Nephrol. 2005. Vol. 16. P. 2449–2455.
28. Sarnak M.J., Levey A.S., Schoolwerth A.C. et al. Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention // Circulation. 2003. Vol. 108. P. 2154–2169.
29. Schmidt R.J., Baylis C. Total nitric oxide production is low in patients with chronic renal renal disease // Kidney Int. 2000. Vol. 58. №. 3. P. 1261–1266.
30. Schwedhelm E., Böger R.H. The role of asymmetric and symmetric dimethylarginines in renal disease // Nat. Rev. Nephrol. 2011. Vol. 7. № 5. P. 275–285.
31. Sebekova K., Spustova V., Opatrny K. Jr. et al. Serotonin and 5-hydroxyindole-acetic acid // Bratisl. Lek Listy. 2001. Vol. 102. № 8. P. 351–356.
32. Teerlink T. Determination of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine in biological samples by HPLC // Meth. Mol. Med. 2002. Vol. 108. P. 263–274.
33. Xiao S., Wagner L., Schmidt R.J. et al. Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease // Kidney Int. 2001. Vol. 59. P. 1466–1472.
34. Zoccali C., Bode-Boger S.M., Mallamaci F. et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study // Lancet. 2001. Vol. 358. P. 2113– 2117.
35. Zoccali C., Malamaci F., Tripepi G. Asymmetric dimethylarginine (ADMA) as a cardiovascular risk factor in end-state renal disease (ESRD) // Eur. J. Clin. Pharmacol. 2006. Vol. 62. Suppl. 13. P. 131–135.
36. Zoccali C., Mallamaci F., Parlongo S. et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease // Circulation. 2002. Vol. 105. P. 1354–1359.
Review
For citations:
Gilinsky M.A., Anokhin S.I., Koroleva S.A., Latysheva T.V., Petrakova G.M., Suhovershin R.A. Blood methylarginines and disturbed regulation of nitric oxide bioavailability in patients of hemodialysis. Nephrology and Dialysis. 2012;14(2):102-108. (In Russ.)
Views:
7
Email this article 