Disease relevance of N-Monomethyl-L-arginine

• Vascular effects of vitamin C (25 mg/min IA) and placebo were determined at rest and during reactive hyperemia (causing endothelium-mediated dilation) before and after intra-arterial infusion of N-monomethyl-L-arginine (L-NMMA) to inhibit endothelial synthesis of nitric oxide [1].
• In a cell-based iNOS assay (A-172 astrocytoma cells) the inhibitors had low-nanomolar IC(50) values and thus were >1,000-fold more potent than the substrate-based direct iNOS inhibitors 1400W and N-methyl-l-arginine [2].
• Overexpression of dimethylarginine dimethylaminohydrolase (DDAH), which metabolizes the endogenous inhibitors of NO synthesis asymmetric dimethylarginine and N-monomethyl-L-arginine, results in C6 gliomas with enhanced growth rate compared with wild type [3].
• Oral treatment of rats with N-methyl-l -arginine acetate (l -NMA), beginning at peak disease on day 11 postimmunization, results in significant prolongation of disease and an alteration in the presentation of clinical symptoms from that of solely hind limb paresis/paralysis to severe fore limb involvement as well [4].
• When cocultured with infected murine neuroblastoma N18 cells, gamma interferon-activated RAW 264.7 cells also efficiently hindered JEV replication in contiguous bystanders, and this anti-JEV effect could be reversed by an NO synthase (NOS) inhibitor, N-monomethyl-L-arginine acetate [5].

High impact information on N-Monomethyl-L-arginine

• NO was released from the hepatic vasculature in a time-dependent manner, and administration of N-monomethyl-L-arginine reduced NO release and increased portal pressure [6].
• We also analyzed IRP1 mRNA levels by Northern blotting and found a decrease in IRP1 mRNA expression after stimulation with IFN-gamma plus lipopolysaccharide, which was abrogated in the presence of N-monomethyl-l-arginine [7].
• Down-regulation of IRP1 protein levels was correlated with the amount of NO produced and was partially abolished by the NO synthase (NOS) inhibitor N-monomethyl-l-arginine [7].
• Addition of N-methyl-L-arginine (NMA), an NO synthase inhibitor, to the medium inhibited NO production by 90% of all stimulated cells, partially reduced doubling time of cells stimulated with LPS or IFN-gamma, and partially increased viability and growth rates in those exposed to both LPS and IFN-gamma [8].
• The responses also were antagonized by atropine (10(-7) mol/L, n = 6), which inhibits release of endothelium-derived relaxing factor (EDRF), and by N-monomethyl-L-arginine (10(-5) mol/L, n = 6), a specific blocker of nitric oxide formation (primary relaxing factor responsible for acetylcholine vasorelaxation) [9].

Chemical compound and disease context of N-Monomethyl-L-arginine

• Nitric oxide synthase was verified as the source of NO in rats with septic shock by pre-administration of the competitive inhibitor N-monomethyl-L-arginine, resulting in reduced enhancement [10].
• Toxic acute renal failure in the rat: effects of L-arginine and N-methyl-L-arginine on renal function [11].

Biological context of N-Monomethyl-L-arginine

• It was demonstrated that HA induced apoptosis in DCs and that induction of apoptosis was dependent on the production of NO because it was entirely inhibited by N-monomethyl-L-arginine [12].
• After each treatment, glomerular filtration rate (GFR), renal plasma flow, and filtration fraction were measured before and after blockade of nitric oxide (NO) by intravenous administration of N-monomethyl-L-arginine-acetate (L-NMMA) [13].
• Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N -monomethyl-L-arginine (NMMA), lipids and body composition were measured [14].
• The NO synthase inhibitor N-monomethyl-L-arginine blocked the inhibitory Arg effect and the NO donor S-nitroso-acetylpenicillamine mimicked it, indicating that high levels of NO block the up-regulation of CPD [15].
• 2. In both groups of rats the analogues (N-monomethyl-L-arginine (L-NMMA) and N-nitro-L-arginine methyl ester (L-NAME)) enhanced hypoxic vasoconstriction [16].

Anatomical context of N-Monomethyl-L-arginine

• Killing of T cells in vitro is blocked by Abs to IFN-gamma, TNF, CD120a, or CD120b, or N-methyl-L-arginine [17].
• Fibroblasts were incubated in the presence or the absence of 0.5 mM S-methyl-isothio-uronium or 0.5 mM N-monomethyl-L-arginine, both competitive inhibitors of NO synthase [18].
• N-monomethyl-L-arginine (L-NMA), a NOS inhibitor, partially inhibited NK cell lysis of four different target cells (<40% inhibition at 500 microM L-NMA), but not granule release following coculture with target cells, or Fas ligand induction following cross-linking with anti-CD16 mAb [19].
• Addition of N-methyl-L-arginine, an NO synthase inhibitor, abrogated much of the cytotoxicity and genotoxicity in both target and macrophages cells, verifying the role of NO in the induction of these responses [20].
• Radial artery flow-mediated dilation (FMD), before and after the intra-arterial infusion of N-monomethyl-L-arginine (L-NMMA), to block NO synthase, and the response to sublingual glyceril trinitrate (GTN, 25 mug) were measured at baseline and after the two treatment periods as a change in artery diameter (computerized system from ultrasound scans) [21].

Associations of N-Monomethyl-L-arginine with other chemical compounds

• The inhibition of DNA synthesis by IL-1beta was completely abrogated when NO production was inhibited by N-monomethyl-L-arginine (NMA), a competitive inhibitor of iNOS [22].
• The enhanced accessory function was suppressed by blockade mAbs to B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor [23].
• However, despite elevated NO production by murine cells, blockage of NO synthesis with the l-arginine analogue N-monomethyl-l-arginine only partially rescued chlamydial growth, suggesting the presence of another IFN-gamma-inducible antichlamydial mechanism unique to murine cells [24].
• Nitric oxide (NO) protects HUVECs from apoptosis in response to various stimuli including serum-deprivation; however, the NO synthase inhibitor N-monomethyl-l-arginine, did not abolish inhibition of caspase-3 activation or PARP cleavage by spironolactone [25].
• Cardiac myocyte cultures were obtained from neonatal Wistar rat hearts, infected with T. cruzi, and treated with IL-1beta, TNF-alpha, IFN-gamma, or N-monomethyl-L-arginine (L-NAME) for 72 h [26].

Gene context of N-Monomethyl-L-arginine

• Further, n-monomethyl-L-arginine (n-MMA) and a soluble TNF-receptor I (TNFRI-IgG) blocked bacterial growth and NO synthesis [27].
• For these reasons, after the identification of N-methyl-L-arginine (L-NMA) as the first inhibitor of NO biosynthesis, design of selective NOS inhibitors has received much attention [28].
• Interferon-gamma release was not up-regulated by N-monomethyl-L-arginine [29].
• Addition of interleukin-4 (IL-4) or the nitric oxide synthase inhibitor N-monomethyl-l-arginine to peritoneal cells inhibited nitric oxide synthesis and enhanced anti-IgE-mediated mast cell degranulation, measured as serotonin release [30].
• NO production was effectively blocked by IL-6 as well as by N-monomethyl-l-arginine (l-NMMA) [31].

Analytical, diagnostic and therapeutic context of N-Monomethyl-L-arginine

• Previously, we reported that oral administration of the NO synthase inhibitor N-methyl-L-arginine acetate (L-NMA) to recovered rats precipitated a second episode of disease in 100% of animals [32].
• METHODS: Recombinant human IL-1beta and NOS inhibitors with different selectivity for inducible NOS (N-monomethyl-L-arginine [L-NMA], N-iminoethyl-L-ornithine [L-NIO], and S-methylisothiourea [SMT]) were simultaneously administered in rats by a single intraarticular injection in each knee [33].
• METHODS: Thirteen young healthy subjects finished an exhaustive bicycle exercise protocol while they were infused placebo or the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) on two separate days in a randomized, double blind cross-over design [34].
• Cardiovascular effects were evaluated before and after microinjection of the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG: 1 nmol) or the NO synthase (NOS) inhibitors N -monomethyl-l-arginine (l-NMMA: 10, 33 and 100 nmol) and N-nitro-l-arginine methyl ester (l-NAME: 10, 33 and 100 nmol) [35].
• Carrageenan was injected into the plantar surface of the hind paw during perfusion of the dialysis catheter with modified Ringer's solution or N-monomethyl-L-arginine acetate [36].

References