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

• L-NAME increased rapid eye movement (REM) sleep in the control group [6].
• L-NAME and NO2Arg also attenuated some signs of morphine dependence, as assessed by naloxone (2 mg/kg)-precipitated withdrawal [7].
• L-NAME (30 mg/kg) and L-arginine (1000 mg/kg) were also tested for ability to depress or stimulate locomotor activity in the absence of amphetamine [8].
• In experiment 2 the effects of pre-treatment (10 min before PCP) with the nitric oxide synthase inhibitor, L-NAME (10 mg/kg s.c.), on the PCP (2 mg/kg)-induced spatial memory deficit was evaluated in the Morris water maze paradigm for reference memory [9].
• L-arginine, but not D-arginine, when coadministered with L-NAME, prevented both the inhibition of NOS activity and the reduction of withdrawal symptoms induced by L-NAME in morphine-withdrawn animals [10].

High impact information on L-NAME

• L-NAME, an eNOS inhibitor, blocked myr-Akt-mediated vasodilatation [11].
• CGRP-induced relaxations are inhibited by a CGRP-R antagonist (CGRP(8-37)), a soluble guanylate cyclase inhibitor (LY(83583)), and a nitric oxide synthase inhibitor (L-NAME) [12].
• The NOS inhibitor L-NAME, the NO scavenger PTIO, the sGC inhibitor ODQ, and methylene blue, which inhibits NOS and guanylate cyclase, each caused the disorganization of retinal projections and extension of photoreceptor axons beyond their normal synaptic layers in vitro [13].
• Anandamide (1 microM) vasodilates juxtamedullary afferent arterioles perfused in vitro; the vasodilation can be blocked by nitric oxide (NO) synthase inhibition with L-NAME (0.1 mM) or CB1 receptor antagonism with SR 141716A (1 microM), but not by indomethacin (10 microM) [14].
• L-NAME increased blood pressure and NE turnover rate in several brain nuclei of both control and 5/6 nephrectomized rats [15].

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

• Reduction in oxygen uptake and increases in intracranial pressure and CSF lactate were blocked by pretreatment with L-NAME, an inhibitor of nitric oxide synthase [21].
• Of particular significance, these cells exhibit a high level of nitric oxide synthase (NOS)-dependent free radical production, and simultaneous treatment of cells with the NOS inhibitor L-NAME resulted in telomere elongation and prevention of apoptosis [22].
• There was some direct activation of mast cells with L-NAME (independent of endothelium) inasmuch as intracellular calcium and oxidative stress increased within mast cells after L-NAME treatment, and this translated into increased neutrophil adhesion to nonendothelial substrata [23].
• The long bleeding times in BKB2R(-/-) mice also correct with L-NAME and nimesulide therapy [1].
• Histology revealed that mast cell degranulation occurred only in animals treated with L-NAME but not in animals pretreated with SOD or ketotifen [24].

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

• Stimulation of this nuclear fraction with LPA and the NO donor sodium nitroprusside resulted, respectively, in increased production of nitrite (and eNOS phosphorylation) and cGMP; these separate responses were also correspondingly blocked by NOS inhibitor L-NAME and soluble guanylate cyclase inhibitor ODQ [31].
• Furthermore, antiapoptotic and caspase suppressive effects of TNF-alpha on osteoclasts were abolished by L-NAME [32].
• Both NO release and apoptosis could be inhibited by neutralizing anti-IL-1beta antibody or the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME), demonstrating the requirement for IL-1beta-mediated NO release in silica-induced apoptosis [33].
• In contrast, SHR, 2-K 1C Goldblatt hypertensive rats and nitric oxide-deficient (L-NAME-treated) hypertensive rats do not exhibit an ET-1 component [34].
• Inhibition with L-NAME occurred despite high levels of NO generated by iNOS, and exogenously supplied NO induced HIV gene expression only weakly, suggesting that cNOS had the greater influence on proviral gene induction [35].

Analytical, diagnostic and therapeutic context of L-NAME

• Finally, using reverse transcriptase-polymerase chain reaction, we have observed that a suboptimal induction of NOS-II mRNA expression in T67 cells was enhanced by vanadate (or L-NAME) and inhibited by genistein [36].
• Death at one month was 27% in the L-NAME group vs. 67% in the control group (p=0.008) [37].
• Significant constriction was observed in arterioles (to 70.0% of initial diameter) and large venules (to 76.6% of initial diameter) after 20 min of suffusion with L-NAME, an inhibitor of NO synthesis [38].
• Ovalbumin inhalation (3 mg/ml, 1 minute) challenge caused significant microvascular leakage in all airways portions, which was significantly suppressed in a dose-dependent manner by pretreatment with intravenous injection of L-NAME (1 and 10 mg/kg) but not with the inactive enantiomer D-NAME (10 mg/kg) [39].
• Time on IABP and time on mechanical ventilation were significantly shorter in the L-NAME group [37].

References