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Chemical Compound Review

L-NAME     methyl(2S)-2-amino-5-[(amino- nitramido...

Synonyms: AmbotzHAA5810, Tocris-0665, CHEMBL7890, BSPBio_001221, KBioGR_000561, ...
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Disease relevance of L-NAME

  • Treatment with L-NAME (NG-mono-methyl-L-arginine ester) or nimesulide shortens the thrombosis time [1].
  • Pressure natriuresis in AT(2) receptor-deficient mice with L-NAME hypertension [2].
  • In this brief overview, I review some of the literature that clearly supports this contention, particularly the dramatically beneficial effects of oral L-NAME administration to animals with colitis induced by trinitrobenzene sulphonic acid (TNBS) [3].
  • Immunoblotting indicated that insulin stimulated the phosphorylation of ERK1/2 after 5 min and 1 h, and that this was completely abolished by pertussis toxin, but insensitive to the nitric oxide synthase inhibitor L-NAME [4].
  • Pathohistological study demonstrated increased pericardiac fibrosis and coronary arterial injury score in the L-NAME group in a dose-dependent manner [5].

Psychiatry related information on L-NAME


High impact information on L-NAME


Chemical compound and disease context of L-NAME

  • Functional studies have previously demonstrated a reduction in tumour blood flow with selective inhibitors of nitric oxide (NO) synthesis, L-NAME (NG-nitro-L-arginine-methylester) and L-NMMA (NG-monomethyl-L-arginine), when administered locally to tumours derived from murine colon 26 adenocarcinoma and B16 melanoma cells [16].
  • RESULTS: Despite a significant increase in plasma arginine (P = 0.001) and a reduction in intimal hyperplasia (P = 0.003) with L-arginine, neither agent had a significant effect on reendothelialization at 4 weeks (controls = 36 +/- 4%, L-arginine = 43 +/- 3%, L-NAME = 33 +/- 4%; NS) [17].
  • Nevertheless, NAC administration failed to attenuate renal function and morphology in a rat model of acute renal failure with selective outer medullary hypoxic injury, induced by indomethacin, L-NAME and iothalamate [18].
  • 2. L-NAME (10 mg kg-1 i.v.) greatly reduced the increase in FVC induced by hypoxia or adenosine, as we have shown before, but had no effect on the increase in FVC evoked by SNP [19].
  • Hydralazine, another vasodilator without effects on NO or platelets, also failed to prevent glomerular thrombosis in rats given LPS + L-NAME [20].

Biological context of L-NAME


Anatomical context of L-NAME

  • In vivo, in the rat mesentery, thrombin (0.5 U/ml) or N(G)-nitro-L-arginine-methyl ester (50 microM) significantly increased venular leukocyte rolling and adherence, which were also significantly (P < 0.01) attenuated by ONOO (800 nM) accompanied by reduced P-selectin expression on the endothelial cell surface [25].
  • Systemic administration of the nitric oxide (NO) synthase inhibitor Nomega-nitro--arginine methyl ester (L-NAME) to rabbits bearing a corneal implant blocked vascular endothelial growth factor (VEGF), but not basic fibroblast growth factor (bFGF)-induced angiogenesis [26].
  • L-NAME did not induce neutrophil-endothelium interactions in the absence of mast cells, but the addition of mast cells in a ratio as low as 1:50 mast cells to neutrophils was sufficient to induce a large increase in neutrophil adhesion to endothelium within 20 to 25 minutes [23].
  • The objective of this study was to elucidate the mechanism (or mechanisms) that promote the L-NAME-induced leukocyte response [24].
  • Superfusion of the rat mesentery with either thrombin or L-NAME consistently and significantly increased the number of rolling, adhering, and transmigrated leukocytes [27].

Associations of L-NAME with other chemical compounds

  • In the present study, we evaluated the effects of L-arginine and L-NAME on blood pressure and SNS activity-in Sprague Dawley 5/6 nephrectomized or sham-operated rats [15].
  • The effects of insulin and IGF-1 were completely blocked by inhibitors of either tyrosine kinase (genestein) or nitric oxide synthase (L-NAME) [28].
  • As measured by three-color flow cytometry, there was a 56+/-11% increase in the number of P selectin- positive platelets in the nonbiotinylated population treated with L-NAME as compared to control [29].
  • Two weeks after the operation, hyperconstrictive responses to intracoronary serotonin and neointimal formation were noted at the IL-1beta-treated site, and both responses were significantly greater at the site cotreated with either L-NAME or aminoguanidine [30].
  • Nitric oxide synthesis was inhibited with L-NAME and leukocyte adhesion was observed over the first 60 min [24].

Gene context of L-NAME


Analytical, diagnostic and therapeutic context of L-NAME


  1. Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin. Shariat-Madar, Z., Mahdi, F., Warnock, M., Homeister, J.W., Srikanth, S., Krijanovski, Y., Murphey, L.J., Jaffa, A.A., Schmaier, A.H. Blood (2006) [Pubmed]
  2. Pressure natriuresis in AT(2) receptor-deficient mice with L-NAME hypertension. Obst, M., Gross, V., Janke, J., Wellner, M., Schneider, W., Luft, F.C. J. Am. Soc. Nephrol. (2003) [Pubmed]
  3. Inducible nitric oxide synthase: a little bit of good in all of us. Kubes, P. Gut (2000) [Pubmed]
  4. A role for heterotrimeric GTP-binding proteins and ERK1/2 in insulin-mediated, nitric-oxide-dependent, cyclic GMP production in human umbilical vein endothelial cells. Konopatskaya, O., Shore, A.C., Tooke, J.E., Whatmore, J.L. Diabetologia (2005) [Pubmed]
  5. Apoptosis, coronary arterial remodeling, and myocardial infarction after nitric oxide inhibition in SHR. Ono, Y., Ono, H., Matsuoka, H., Fujimori, T., Frohlich, E.D. Hypertension (1999) [Pubmed]
  6. Influence of temporomandibular joint pain on sleep patterns: role of nitric oxide. Schütz, T.C., Andersen, M.L., Tufik, S. J. Dent. Res. (2004) [Pubmed]
  7. Inhibition of nitric oxide synthase attenuates the development of morphine tolerance and dependence in mice. Majeed, N.H., Przewłocka, B., Machelska, H., Przewłocki, R. Neuropharmacology (1994) [Pubmed]
  8. Nitric oxide synthase inhibition blocks amphetamine-induced locomotor activity in mice. Celik, T., Zaglí, U., Kayír, H., Uzbay, I.T. Drug and alcohol dependence. (1999) [Pubmed]
  9. Effects of phencyclidine on spatial learning and memory: nitric oxide-dependent mechanisms. Wass, C., Archer, T., Pålsson, E., Fejgin, K., Klamer, D., Engel, J.A., Svensson, L. Behav. Brain Res. (2006) [Pubmed]
  10. Correlation between brain nitric oxide synthase activity and opiate withdrawal. Leza, J.C., Lizasoain, I., Cuéllar, B., Moro, M.A., Lorenzo, P. Naunyn Schmiedebergs Arch. Pharmacol. (1996) [Pubmed]
  11. Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. Luo, Z., Fujio, Y., Kureishi, Y., Rudic, R.D., Daumerie, G., Fulton, D., Sessa, W.C., Walsh, K. J. Clin. Invest. (2000) [Pubmed]
  12. Involvement of calcitonin gene-related peptide in the modulation of human myometrial contractility during pregnancy. Dong, Y.L., Fang, L., Kondapaka, S., Gangula, P.R., Wimalawansa, S.J., Yallampalli, C. J. Clin. Invest. (1999) [Pubmed]
  13. Nitric oxide and cyclic GMP regulate retinal patterning in the optic lobe of Drosophila. Gibbs, S.M., Truman, J.W. Neuron (1998) [Pubmed]
  14. Production and physiological actions of anandamide in the vasculature of the rat kidney. Deutsch, D.G., Goligorsky, M.S., Schmid, P.C., Krebsbach, R.J., Schmid, H.H., Das, S.K., Dey, S.K., Arreaza, G., Thorup, C., Stefano, G., Moore, L.C. J. Clin. Invest. (1997) [Pubmed]
  15. Nitric oxide (NO) modulates the neurogenic control of blood pressure in rats with chronic renal failure (CRF). Ye, S., Nosrati, S., Campese, V.M. J. Clin. Invest. (1997) [Pubmed]
  16. Induction of nitric oxide synthase in the neo-vasculature of experimental tumours in mice. Buttery, L.D., Springall, D.R., Andrade, S.P., Riveros-Moreno, V., Hart, I., Piper, P.J., Polak, J.M. J. Pathol. (1993) [Pubmed]
  17. L-arginine and L-NAME have no effects on the reendothelialization process after arterial balloon injury. Six, I., Van Belle, E., Bordet, R., Corseaux, D., Callebert, J., Dupuis, B., Bauters, C., Bertrand, M.E. Cardiovasc. Res. (1999) [Pubmed]
  18. N-acetylcysteine ameliorates renal microcirculation: studies in rats. Heyman, S.N., Goldfarb, M., Shina, A., Karmeli, F., Rosen, S. Kidney Int. (2003) [Pubmed]
  19. Cellular mechanisms by which adenosine induces vasodilatation in rat skeletal muscle: significance for systemic hypoxia. Bryan, P.T., Marshall, J.M. J. Physiol. (Lond.) (1999) [Pubmed]
  20. Exogenous nitric oxide prevents endotoxin-induced glomerular thrombosis in rats. Westberg, G., Shultz, P.J., Raij, L. Kidney Int. (1994) [Pubmed]
  21. Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide. Tureen, J. J. Clin. Invest. (1995) [Pubmed]
  22. Induction of nitric oxide synthase-dependent telomere shortening after functional inhibition of Hsp90 in human tumor cells. Compton, S.A., Elmore, L.W., Haydu, K., Jackson-Cook, C.K., Holt, S.E. Mol. Cell. Biol. (2006) [Pubmed]
  23. A balance between nitric oxide and oxidants regulates mast cell-dependent neutrophil-endothelial cell interactions. Niu, X.F., Ibbotson, G., Kubes, P. Circ. Res. (1996) [Pubmed]
  24. Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. Kubes, P., Kanwar, S., Niu, X.F., Gaboury, J.P. FASEB J. (1993) [Pubmed]
  25. Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats. Lefer, D.J., Scalia, R., Campbell, B., Nossuli, T., Hayward, R., Salamon, M., Grayson, J., Lefer, A.M. J. Clin. Invest. (1997) [Pubmed]
  26. Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. Ziche, M., Morbidelli, L., Choudhuri, R., Zhang, H.T., Donnini, S., Granger, H.J., Bicknell, R. J. Clin. Invest. (1997) [Pubmed]
  27. C-peptide inhibits leukocyte-endothelium interaction in the microcirculation during acute endothelial dysfunction. Scalia, R., Coyle, K.M., Levine, B.J., Booth, G., Lefer, A.M. FASEB J. (2000) [Pubmed]
  28. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. Zeng, G., Quon, M.J. J. Clin. Invest. (1996) [Pubmed]
  29. Nitric oxide released from activated platelets inhibits platelet recruitment. Freedman, J.E., Loscalzo, J., Barnard, M.R., Alpert, C., Keaney, J.F., Michelson, A.D. J. Clin. Invest. (1997) [Pubmed]
  30. Vasculoprotective role of inducible nitric oxide synthase at inflammatory coronary lesions induced by chronic treatment with interleukin-1beta in pigs in vivo. Fukumoto, Y., Shimokawa, H., Kozai, T., Kadokami, T., Kuwata, K., Yonemitsu, Y., Kuga, T., Egashira, K., Sueishi, K., Takeshita, A. Circulation (1997) [Pubmed]
  31. Nitric oxide signaling via nuclearized endothelial nitric-oxide synthase modulates expression of the immediate early genes iNOS and mPGES-1. Gobeil, F., Zhu, T., Brault, S., Geha, A., Vazquez-Tello, A., Fortier, A., Barbaz, D., Checchin, D., Hou, X., Nader, M., Bkaily, G., Gratton, J.P., Heveker, N., Ribeiro-da-Silva, A., Peri, K., Bard, H., Chorvatova, A., D'Orléans-Juste, P., Goetzl, E.J., Chemtob, S. J. Biol. Chem. (2006) [Pubmed]
  32. Involvement of iNOS-dependent NO production in the stimulation of osteoclast survival by TNF-alpha. Lee, S.K., Huang, H., Lee, S.W., Kim, K.H., Kim, K.K., Kim, H.M., Lee, Z.H., Kim, H.H. Exp. Cell Res. (2004) [Pubmed]
  33. Crucial role of interleukin-1beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice. Srivastava, K.D., Rom, W.N., Jagirdar, J., Yie, T.A., Gordon, T., Tchou-Wong, K.M. Am. J. Respir. Crit. Care Med. (2002) [Pubmed]
  34. Endothelin and endothelin antagonists in hypertension. Schiffrin, E.L. J. Hypertens. (1998) [Pubmed]
  35. A defect in HIV-1 transgenic murine macrophages results in deficient nitric oxide production. Dickie, P., Roberts, A., Lee, R. J. Leukoc. Biol. (2001) [Pubmed]
  36. Rapid inactivation of NOS-I by lipopolysaccharide plus interferon-gamma-induced tyrosine phosphorylation. Colasanti, M., Persichini, T., Cavalieri, E., Fabrizi, C., Mariotto, S., Menegazzi, M., Lauro, G.M., Suzuki, H. J. Biol. Chem. (1999) [Pubmed]
  37. LINCS: L-NAME (a NO synthase inhibitor) in the treatment of refractory cardiogenic shock: a prospective randomized study. Cotter, G., Kaluski, E., Milo, O., Blatt, A., Salah, A., Hendler, A., Krakover, R., Golick, A., Vered, Z. Eur. Heart J. (2003) [Pubmed]
  38. Tracheal microvascular responses to inhibition of nitric oxide synthesis in anesthetized rats. Corboz, M.R., Ballard, S.T., Inglis, S.K., Taylor, A.E. Am. J. Respir. Crit. Care Med. (1996) [Pubmed]
  39. Endogenous nitric oxide modifies antigen-induced microvascular leakage in sensitized guinea pig airways. Miura, M., Ichinose, M., Kageyama, N., Tomaki, M., Takahashi, T., Ishikawa, J., Ohuchi, Y., Oyake, T., Endoh, N., Shirato, K. J. Allergy Clin. Immunol. (1996) [Pubmed]
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