Non-Enzymatic Production of Nitric Oxide (NO) from NO Synthase Inhibitors

Moroz, Leonid L.; Norby, Shong Wan; Cruz, Lou Ann; Sweedler, Jonathan V.; Gillette, Rhanor; Clarkson, R. B.

doi:10.1006/bbrc.1998.9810

Cited by 61 publications

(47 citation statements)

References 33 publications

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“…Similar parallel effects of L-arginine and L-NAME were reported previously under various (patho)physiological conditions (Henningsson et al, 2000;Vasilijević et al, 2007a). These analogous effects were attributed to the action of NO originating from non-enzymatic (Moroz et al, 1998) and iNOS-mediated (Henningsson et al, 2000) production in the presence of NOS inhibitors, or they may be related to other NO-independent metabolic effects of an L-arginine analog (Krippeit-Drews et al, 1996). Moreover, following in vivo administration of NOS inhibitors, the response may result from their systemic effects, and not only from local, peripheral effects (Bult et al, 1990;Jun et al, 1995).…”

Section: P<0001 Pgc-1α/ppars In Skeletal Muscle In the Coldsupporting

confidence: 84%

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Stančić

Buzadžić

Korać

et al. 2013

Journal of Experimental Biology

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SUMMARYThis study examined the molecular basis of energy-related regulatory mechanisms underlying metabolic recruitment of skeletal muscle during cold acclimation and possible involvement of the L-arginine/nitric oxide-producing pathway. Rats exposed to cold (4±1°C) for periods of 1, 3, 7, 12, 21 and 45 days were divided into three groups: untreated, L-arginine treated and N ω -nitro-Larginine methyl ester (L-NAME) treated. Compared with controls (22±1°C), there was an initial increase in the protein level of 5′-AMP-activated protein kinase α (day 1), followed by an increase in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and peroxisome proliferator-activated receptors (PPARs): PPARα and PPARγ from day 1 and PPARδ from day 7 of cold acclimation. Activation of the PGC-1α/PPAR transcription program was accompanied by increased protein expression of the key metabolic enzymes in β-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation, with the exceptions in complex I (no changes) and ATP synthase (decreased at day 1). Cold did not affect hexokinase and GAPDH protein levels, but increased lactate dehydrogenase activity compared with controls (1-45 days). L-arginine sustained, accelerated and/or intensified cold-induced molecular remodeling throughout cold acclimation. L-NAME exerted phase-dependent effects: similar to L-arginine in early cold acclimation and opposite after prolonged cold exposure (from day 21). It seems that upregulation of the PGC-1α/PPAR transcription program early during cold acclimation triggers the molecular recruitment of skeletal muscle underlying the shift to more oxidative metabolism during prolonged cold acclimation. Our results suggest that nitric oxide has a role in maintaining the skeletal muscle oxidative phenotype in late cold acclimation but question its role early in cold acclimation.

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Section: P<0001 Pgc-1α/ppars In Skeletal Muscle In the Coldsupporting

confidence: 84%

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Stančić

Buzadžić

Korać

et al. 2013

Journal of Experimental Biology

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“…However, there are several reports, with different model systems, concerning the same effect of L-NAME treatment as that seen after L-arginine treatment. Conflicting observations in experiments with the NOSs inhibitor L-NAME are explained by non-enzymatic production of NO during incubation with L-NAME in the presence of NADPH, GSH and ascorbate (Moroz et al, 1998). Henningsson et al (Henningsson et al, 2000) showed that chronic L-NAME treatment in diabetic rats blocked constitutive NOSs that evoked iNOS-derived NO production to compensate for NO level, while Krippeit-Drews et al (KrippeitDrews et al, 1996) reported that L-NAME can also act directly, not via intracellular messengers.…”

Section: Discussionmentioning

confidence: 92%

Antioxidative defence alterations in skeletal muscle during prolonged acclimation to cold: role ofl-arginine/NO-producing pathway

Petrović

Buzadžić

Korać

et al. 2008

Journal of Experimental Biology

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SUMMARYEarly in cold acclimation (1-7·days), heat is produced by shivering, while late in cold acclimation (12-45·days), skeletal muscle contributes to thermogenesis by tissue metabolism other than contractions. Given that both thermogenic phases augment skeletal muscle aerobic power and reactive species production, we aimed in this study to examine possible changes in skeletal muscle antioxidative defence (AD) during early and late cold acclimation with special emphasis on the influence of the Larginine/nitric oxide (NO)-producing pathway on the modulation of AD in this tissue. Adult Mill Hill hybrid hooded rat males were divided into two main groups: a control group, which was kept at room temperature (22±1°C), and a group maintained at 4±1°C for 45·days. The cold-acclimated group was divided into three subgroups: untreated, L-arginine treated and N -nitro-L-arginine methyl ester (L-NAME) treated. The AD parameters were determined in the gastrocnemius muscle on day 1, 3, 7, 12, 21 and 45 of cold acclimation. The results showed an improvement of skeletal muscle AD in both early and late cold acclimation. Clear phasedependent changes were seen only in copper, zinc superoxide dismutase activity, which was increased in early cold acclimation but returned to the control level in late acclimation. In contrast, there were no phase-dependent changes in manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, the activities of which were increased during the whole cold exposure, indicating their engagement in both thermogenic phases. L-Arginine in early cold acclimation accelerated the cold-induced AD response, while in the late phase it sustained increases achieved in the early period. L-NAME affected both early and late acclimation through attenuation and a decrease in the AD response. These data strongly suggest the involvement of the L-arginine/NO pathway in the modulation of skeletal muscle AD.

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“…NO has also been reported to be generated in biological systems by a nonenzymatic pathway, which involves chemical reduction of inorganic nitrite (9 -13). Nonenzymatic NO generation has been demonstrated in vivo, for example, in the mouth (14), stomach (15), on the surface of the skin (16), in the ischemic heart (12), and in infected nitrite-containing urine (17), as well as under certain conditions involving NOS inhibitors (9) and substrates (10).…”

mentioning

confidence: 99%

Whole body detection and imaging of nitric oxide generation in mice following cardiopulmonary arrest: Detection of intrinsic nitrosoheme complexes

Kuppusamy

Shankar

Roubaud

et al. 2001

Magnetic Resonance in Med

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Ischemic tissues generate nitric oxide (NO) by direct reduction of tissue nitrite under the acidic conditions that occur during ischemia. In view of the important implications of this enzymeindependent mechanism of NO generation on the pathogenesis and treatment of tissue injury, the NO formation in mice subjected to cardiopulmonary arrest was measured and imaged. Real-time measurement of NO generation was performed by detection of naturally generated NO-heme complexes in tissues using L-band electron paramagnetic resonance (EPR) spectroscopy. To distinguish NO generated from nitrite, animals were labeled with isotopically enriched 15 N-nitrite. Mice were infused with nitrite (70 mg/kg, intravenous), cardiopulmonary arrest induced by an overdose of phenobarbital, and transferred to the EPR resonator. Measurements of NO generation were performed on the intact animal at the levels of the head, thorax, and abdomen. At the end of 3 hr, major organs were isolated and analyzed for their NO signal. The NO complexes were found to have maximum levels in lung, heart, and liver. Three-dimensional spatial mapping of the NO complex in the intact animal subjected to cardiopulmonary arrest was performed using EPR imaging techniques. The images also confirmed the maximum formation in the lungs, heart, and liver. The present data reveal that mice subjected to cardiopulmonary arrest generate large amounts of NO, which is nitrite mediated. The observed signal was largely due to heme-bound NO, which accounted for the high concentrations found in these organs. This increased NO formation during cardiopulmonary arrest could contribute to the difficulty of resuscitation after long periods of arrest. Magn Reson Med 45:700 -707, 2001.

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Non-Enzymatic Production of Nitric Oxide (NO) from NO Synthase Inhibitors

Cited by 61 publications

References 33 publications

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Regulatory role of PGC-1alpha/PPARs signaling in skeletal muscle metabolic recruitment during cold acclimation

Antioxidative defence alterations in skeletal muscle during prolonged acclimation to cold: role ofl-arginine/NO-producing pathway

Whole body detection and imaging of nitric oxide generation in mice following cardiopulmonary arrest: Detection of intrinsic nitrosoheme complexes

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