Effects of chronic oral l-arginine administration on the l-arginine/NO pathway in patients with peripheral arterial occlusive disease or c

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• 作者：Jessica Y. Schneider ; Sabine Rothmann ; Frank Schr?der ; Jennifer Langen…
• 关键词：Cardiovascular disease ; Nitric oxide ; Nitrite ; Prostacyclin ; Renal carbonic anhydrase ; Thromboxane
• 刊名：Amino Acids
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：47
• 期：9
• 页码：1961-1974
• 全文大小：586 KB
• 参考文献：Aamand R, Dalsgaard T, Jensen FB, Simonsen U, Roepstorff A, Fago A (2009) Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation. Am J Physiol Heart Circ Physiol 297:H2068–H2074CrossRef PubMed
  Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R, Vallance P (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 23:1455-459CrossRef PubMed
  Ahmetaj-Shala B, Kirkby NS, Knowles R, Al’Yamani M, Mazi S, Wang Z, Tucker AT, Mackenzie L, Armstrong PC, Nüsing RM, Tomlinson JA, Warner TD, Leiper J, Mitchell JA (2015) Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethyl arginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs. Circulation 131:633-42CrossRef PubMed
  Bode-B?ger SM (2006) Effect of arginine supplementation on NO production in man. Eur J Clin Pharmacol 62:91-9CrossRef
  Bode-B?ger SM, B?ger RH, Creutzig A, Tsikas D, Gutzki FM, Alexander K, Fr?lich JC (1994) l -arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy humans subjects. Clin Sci 87:303-10CrossRef PubMed
  Bode-B?ger SM, B?ger RH, Alfke H, Heinzel D, Tsikas D, Creutzig A, Alexander K, Fr?lich JC (1996) l -Arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia. A randomized, controlled study. Circulation 93:85-0CrossRef PubMed
  Bode-B?ger SM, B?ger RH, L?ffler M, Tsikas D, Brabant G, Fr?lich JC (1999) l -Arginine stimulates NO-dependent vasodilation in healthy humans—effects of somatostatin pretreatment. J Invest Med 47:43-0
  B?ger RH (2004) Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the -span class="EmphasisTypeSmallCaps">l -arginine paradox-and acts as a novel cardiovascular risk factor. J Nutr 134:2842S-847SPubMed
  B?hmer A, Gambaryan S, Tsikas D (2014) Human blood samples lack nitric oxide synthase activity. Platelets. doi:10.-109/-9537104.-014.-74024 PubMed
  Brosnan ME, Brosnan JT (2004) Renal arginine metabolism. J Nutr 134:2791S-895SPubMed
  Chobanyan-Jürgens K, Schwarz A, B?hmer A, Beckmann B, Gutzki FM, Michaelsen JT, Stichtenoth DO, Tsikas D (2012) Renal carbonic anhydrases are involved in the reabsorption of endogenous nitrite. Nitric Oxide 26:126-31CrossRef PubMed
  Fitzgerald DJ, Fitzgerald GA (2013) Historical lessons in translational medicine: cyclooxygenase inhibition and P2Y12 antagonism. Circ Res 112:174-94PubMed Central CrossRef PubMed
  F?rstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33:829-37PubMed Central CrossRef PubMed
  Gladwin MT, Raat NJ, Shiva S, Dezfulian C, Hogg N, Kim-Shapiro DB, Patel RP (2006) Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am J Physiol Heart Circ Physiol 291:H2026–H2035CrossRef PubMed
  Hu SD, Li XL, Rezaei R, Meininger CJ, McNeal CJ, Wu G (2015) Safety of long-term dietary supplementation with l -arginine in pigs. Amino Acids 47:925-36CrossRef PubMed
  Innocenti A, Vullo D, Scozzafava A, Supuran CT (2008) Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem 16:7424-428CrossRef PubMed
  Kanno K, Hirata Y, Emori R, Ohta K, Eguchi S, Imai T, Marumo F (1992) l -Arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans. Clin Exp Pharmacol Physiol 19:619-25CrossRef PubMed
  Kayacelebi AA, Willers J, Pham VV, Hahn A, Schneider JY, Rothmann S, Fr?lich JC, Tsikas D (2015a) Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease. Amino Acids. doi:10.-007/?s00726-015-1915-3
  Kayacelebi AA, Langen J, Weigt-Usinger K et al (2015b) Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free l -arginine in humans. Amino Acids. doi:10.-007/?s00726-015-2012-3
  Keimer R, Stutzer FK, Tsikas D, Troost R, Gutzki FM, Fr?lich JC (2003) Lack of oxidative stress during sustained therapy with isosorbide dinitrate and pentaerythrityl tetranitrate in healthy humans: a randomized, double-blind crossover study. J Cardiovasc Pharmacol 41:284-92CrossRef PubMed
  Kielstein A, Tsikas D, Galloway GP, Mendelson JE (2007) Asymmetric dimethylarginine (ADMA)—a modulator of nociception in opiate tolerance and addiction? Nitric Oxide 17:55-9PubMed Central CrossRef PubMed
  Lachmuth JY (2007) The APAV pilot study. l -Arginine in patients
• 作者单位：Jessica Y. Schneider (1)
  Sabine Rothmann (1)
  Frank Schr?der (1)
  Jennifer Langen (2)
  Thomas Lücke (2)
  Fran?ois Mariotti (3) (4)
  Jean Fran?ois Huneau (3) (4)
  Jürgen C. Fr?lich (1)
  Dimitrios Tsikas (1)
  
  1. Centre of Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
  2. Department of Neuropaediatrics, Children’s Hospital, University of Bochum, Bochum, Germany
  3. INRA, CRNH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, 75005, Paris, France
  4. AgroParisTech, CRNH-IdF, UMR914 Nutrition Physiology and Ingestive Behavior, 75005, Paris, France
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

Despite saturation of nitric oxide (NO) synthase (NOS) by its substrate l-arginine (Arg), oral and intravenous supplementation of Arg may enhance NO synthesis, a phenomenon known as “The l-arginine paradox- Yet, Arg is not only a source of NO, but is also a source for guanidine-methylated (N G) arginine derivatives which are all inhibitors of NOS activity. Therefore, Arg supplementation may not always result in enhanced NO synthesis. Concomitant synthesis of N G-monomethyl arginine (MMA), N G,N G-dimethylarginine (asymmetric dimethylarginine, ADMA) and N G,N G′-dimethylarginine (symmetric dimethylarginine, SDMA) from supplemented Arg may outweigh and even outbalance the positive effects of Arg on NO. Another possible, yet little investigated effect of Arg supplementation may be alteration of renal function, notably the influence on the excretion of nitrite in the urine. Nitrite is the autoxidation product of NO and the major reservoir of NO in the circulation. Nitrite and Arg are reabsorbed in the proximal tubule of the nephron and this reabsorption is coupled, at least in part, to the renal carbonic anhydrase (CA) activity. In the present placebo-controlled studies, we investigated the effect of chronic oral Arg supplementation of 10 g/day for 3 or 6 months in patients suffering from peripheral arterial occlusive disease (PAOD) or coronary artery disease (CAD) on the urinary excretion of nitrite relative to nitrate. We determined the urinary nitrate-to-nitrite molar ratio (U_NOxR), which is a measure of nitrite-dependent renal CA activity before and after oral intake of Arg or placebo by the patients. The U_NOxR was also determined in 6 children who underwent the Arg test, i.e., intravenous infusion of Arg (0.5 g Arg/kg bodyweight) for 30 min. Arg was well tolerated by the patients of the three studies. Oral Arg supplementation increased Arg (plasma and urine) and ADMA (urine) concentrations. No appreciable changes were seen in NO (in PAOD and CAD) and prostacyclin and thromboxane synthesis (in PAOD). In the PAOD study, U_NOxR did not change in the Arginine group (480 ± 51 vs 486 ± 50), but fell in the Placebo group (422 ± 67 vs 332 ± 42, P = 0.025). In the CAD study, U_NOxR did not change significantly in the Arginine group (518 ± 77 at start vs 422 ± 40 after 3 months vs 399 ± 66 after 6 months), but fell in the Placebo group (524 ± 69 vs 302 ± 36 vs 285 ± 31; P = 0.025 for 0 vs 3 months). Infusion of Arg tended to decrease the U_NOxR in the children (317 ± 41 vs 208 ± 16, P = 0.06). We propose that oral long-term Arg supplementation prevents loss of NO bioactivity by saving nitrite. The optimum Arg dose needs to be elaborated and is likely to be less than 10 g per day in adults. Orally and intravenously administered arginine was well tolerated by the elderly patients and young children, respectively. Keywords Cardiovascular disease Nitric oxide Nitrite Prostacyclin Renal carbonic anhydrase Thromboxane