scholarly journals Further evidence for the role of nitric oxide in maternal aggression: effects of L-NAME on maternal aggression towards female intruders in Wistar rats

2009 ◽  
pp. 591-598
Author(s):  
S Ankarali ◽  
HC Ankarali ◽  
C Marangoz
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Aggressive Behavior ◽  
Wistar Rats ◽  
No Production ◽  
Maternal Aggression ◽  
Prairie Voles ◽  
Nos Inhibitor ◽  
Oxide Synthase

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG -nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.

Parasite killing in murine malaria does not require nitric oxide production

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 139-143 ◽  
Author(s):  
N. FAVRE ◽  
B. RYFFEL ◽  
W. RUDIN
Keyword(s):  
Nitric Oxide ◽  
Blood Stage ◽  
No Production ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Stage Parasite ◽  
Blood Stage Malaria ◽  
Inducible Nitric Oxide

Nitric oxide (NO) production has been suggested to play a role as effector molecule in the control of the malarial infections. However, the roles of this molecule are debated. To assess whether blood-stage parasite killing is NO dependent, we investigated the course of blood-stage Plasmodium chabaudi chabaudi (Pcc) infections in inducible nitric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, and survival were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not required for protection against malaria in our murine experimental model. However, C57BL/6 mice treated with AG lost their resistance to Pcc infections, suggesting that the requirement for NO production for parasite killing in murine blood-stage malaria might be strain dependent.

scholarly journals Clinical and Serologic Manifestations of Autoimmune Disease in MRL-lpr/lpr Mice Lacking Nitric Oxide Synthase Type 2

1997 ◽  
Vol 186 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Gary S. Gilkeson ◽  
John S. Mudgett ◽  
Michael F. Seldin ◽  
Phil Ruiz ◽  
Audrey A. Alexander ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Immunoblot Analysis ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Renal Vessels ◽  
Dna Antibodies ◽  
Nos Inhibitor ◽  
Oxide Synthase

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL–lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl–arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL–lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL–lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL–lpr/lpr mice to the N4 generation. MRL–lpr/lpr littermates homozygous for disrupted NOS2 (−/−), heterozygous for disrupted NOS2 (+/−), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (−/−) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/−) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (−/−) animals, whereas that of (+/+) was high and (+/−) intermediate. The (−/−) mice developed glomerular and synovial pathology similar to that of the (+/−) and (+/+) mice. However, (−/−) mice and (+/−) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (−/−) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms.

The development of murine cerebral malaria does not require nitric oxide production

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 135-138 ◽  
Author(s):  
N. FAVRE ◽  
B. RYFFEL ◽  
W. RUDIN
Keyword(s):  
Nitric Oxide ◽  
Cerebral Malaria ◽  
Plasmodium Berghei ◽  
No Production ◽  
Survival And Development ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Nitric oxide (NO) production has been suggested to be required for the development of cerebral malaria. However, the importance of this molecule for the appearance of this pathology is debated. To assess whether murine cerebral malaria is NO dependent, we investigated the course of blood-stage Plasmodium berghei ANKA (PbA) infections in inducible nitric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, survival and development of cerebral malaria were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not a crucial factor for the development of murine cerebral malaria.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

2007 ◽  
Vol 292 (4) ◽  
pp. H1995-H2003 ◽  
Author(s):  
Zuo-Hui Shao ◽  
Wei-Tien Chang ◽  
Kim Chai Chan ◽  
Kim R. Wojcik ◽  
Chin-Wang Hsu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Therapeutic Hypothermia ◽  
Optimal Timing ◽  
No Production ◽  
Early Reperfusion ◽  
No Signaling ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Pkc Activation

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 ± 3.4% cell death. Hypothermia induction to 25°C was most protective (14.3 ± 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 ± 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 ± 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor Nω-nitro-l-arginine methyl ester (200 μM) reversed these changes and abrogated hypothermia protection. In addition, the PKCε inhibitor myr-PKCε v1-2 (5 μM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cε; nitric oxide synthase.

Abstract 111: Xanthine Oxidoreductase Plays a Key Role in Nitrate, Nitrite and Nitric Oxide Homeostasis When the Endothelial Nitric Oxide Synthase is Compromised

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Maria Peleli ◽  
Christa Zollbrecht ◽  
Marcelo Montenegro ◽  
Michael Hezel ◽  
Eddie Weitzberg ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Primary Source ◽  
No Production ◽  
Xanthine Oxidoreductase ◽  
Physiological Conditions ◽  
Inorganic Nitrate ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Xanthine oxidoreductase (XOR) is generally known as a source of superoxide production, but this enzyme has also been suggested to mediate NO production via reduction of inorganic nitrate (NO 3 - ) and nitrite(NO 2 - ). This pathway for NO generation is of particular importance during certain pathologies, whereas endothelial NO synthase (eNOS) is the primary source of vascular NO generation under normal physiological conditions. The exact interplay between the NOS and XOR-derived NO is not yet fully elucidated. The aim of the present study was to investigate if eNOS deficiency is partly compensated by XOR upregulation and sensitization of the NO 3 - - NO 2 - - NO pathway. NO 3 - and NO 2 - were similar between naïve eNOS KO and wildtype (wt) mice, but reduced upon chronic treatment with the non-selective NOS inhibitor L-NAME (wt: 25.0±5.2, eNOS KO: 39.2±6.4, L-NAME: 8.2±1.6 μ NO 3 - -, wt: 0.38±0.07, eNOS KO: 0.42±0.04, L-NAME: 0.12±0.02 μ NO 2 - ). XOR function was upregulated in eNOS KO compared with wt mice [(mRNA: wt 1±0.07, eNOS KO 1.38±0.17), (activity: wt 825±54, eNOS KO 1327±280 CLU/mg/min), (uric acid: wt 32.87±1.53, eNOS KO 43.23±3.54 μ)]. None of these markers of XOR activity was increased in nNOS KO and iNOS KO mice. Following acute dose of NO 3 - (10 mg/kg bw, i.p.), the increase of plasma NO 2 - was more pronounced in eNOS KO (+0.51±0.13 μ) compared with wt (+0.22±0.09 μ), and this augmented response in the eNOS KO was abolished by treatment with the highly selective XOR inhibitor febuxostat (FEB). Liver from eNOS KO had higher reducing capacity of NO 2 - to NO compared with wt, and this effect was attenuated by FEB (Δppb of NO: wt +8.7±4.2, eNOS KO +44.2±15.0, wt+FEB +22.2±9.6, eNOS KO+FEB +26.8±10.2). Treatment with FEB increased blood pressure in eNOS KO (ΔMAP:+10.2±5.6 mmHg), but had no effect in wt (ΔMAP:-0.6±3.3 mmHg). Supplementation with NO 3 - (10 mM, drinking water) reduced blood pressure in eNOS KO (ΔMAP: -6.3±2.2 mmHg), and this effect was abolished by FEB (ΔMAP: +1.1±1.9 mmHg). In conclusion, upregulated and altered XOR function in conditions with eNOS deficiency can facilitate the NO 3 - - NO 2 - - NO pathway and hence play a significant role in vascular NO homeostasis.

Nitric oxide-dependent and -independent components of cerebrovasodilation elicited by hypercapnia

1994 ◽  
Vol 266 (2) ◽  
pp. R546-R552 ◽  
Author(s):  
C. Iadecola ◽  
F. Zhang
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Time Course ◽  
Slow Time ◽  
Independent Components ◽  
Arterial Partial Pressure ◽  
Partial Pressure Of Co2 ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Doppler Flowmeter

We studied the effect of nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on the increases in cerebral blood flow (CBF) elicited by stepwise elevations in arterial partial pressure of CO2 (PaCO2) from normocapnia up to 204 mmHg. Rats were anesthetized with halothane and ventilated. CBF was monitored over the parietal cortex using a laser-Doppler flowmeter. Increasing levels of hypercapnia elicited graded elevations in CBF that reached a plateau at PaCO2 = 82 +/- 1 mmHg (CBF +215 +/- 25%; n = 8; P < 0.05, analysis of variance). L-NAME (40 mg/kg i.v.; n = 8), but not nitro-D-arginine methyl ester (n = 8), reduced resting CBF (-42 +/- 4%) and attenuated the increase in CBF elicited by hypercapnia. The attenuation occurred only at PaCO2 40-80 mmHg and was maximal (-75 +/- 8%; P < 0.05) at 54 +/- 2 mmHg. At PaCO2 > or = 100 mmHg, L-NAME (40-80 mg/kg) did not attenuate the response (P > 0.05). Reduction of resting CBF (-50 +/- 4%; n = 6) by administration of chloralose (20-40 mg/kg i.v.) did not attenuate the CBF response to hypercapnia (P > 0.05). We also found that the attenuation by L-NAME of resting CBF (n = 5) and of the cerebrovasodilation elicited by hypercapnia (n = 6) has a relatively slow time course, the effects reaching a maximum 45-60 min after intravenous administration of the drug. We conclude that L-NAME does not attenuate the CBF response to CO2 uniformly at all levels of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Suppression of arthritis by an inhibitor of nitric oxide synthase.

1993 ◽  
Vol 178 (2) ◽  
pp. 749-754 ◽  
Author(s):  
N McCartney-Francis ◽  
J B Allen ◽  
D E Mizel ◽  
J E Albina ◽  
Q W Xie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
No Production ◽  
Streptococcal Cell Wall ◽  
Cell Mediated Immune Response ◽  
A Cell ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Articular Index

Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by NO synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of NG-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease.

scholarly journals Regulatory Role of GSK-3βon NF-κB, Nitric Oxide, and TNF-αin Group A Streptococcal Infection

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Tzu Chang ◽  
Chia-Ling Chen ◽  
Chiou-Feng Lin ◽  
Shiou-Ling Lu ◽  
Miao-Huei Cheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mouse Model ◽  
Group A Streptococcus ◽  
Glycogen Synthase ◽  
Critical Issue ◽  
No Production ◽  
Group A ◽  
Oxide Synthase

Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β(GSK-3β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3βin GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3βoccurred after GAS infection, and inhibition of GSK-3βreduced iNOS expression and NO production. Furthermore, GSK-3βinhibitors reduced NF-κB activation and subsequent TNF-αproduction, which indicates that GSK-3βacts upstream of NF-κB in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3βinhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-αand improved the survival rate. The inhibition of GSK-3βto moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

scholarly journals 108 THE ROLE OF NITRIC OXIDE SYNTHASE IN IN VITRO DEVELOPMENT OF BOVINE OOCYTES AND PRE-IMPLANTATION EMBRYOS

2005 ◽  
Vol 17 (2) ◽  
pp. 204
Author(s):  
A.K. Kadanga ◽  
D. Tesfaye ◽  
S. Ponsuksili ◽  
K. Wimmers ◽  
M. Gilles ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Culture Medium ◽  
Bovine Embryos ◽  
Nos Inhibitor ◽  
Blastocyst Rate ◽  
Oxide Synthase ◽  
Vitro Development ◽  
Bovine Oocytes

Nitric oxide (NO) is a free radical that serves as a key-signal molecule in various physiological processes including reproduction. Four isoforms of nitric oxide synthase (NOS) have been characterized: endothelial (eNOS), inducible (iNOS), neuronal (nNOS), and mitochondrial (mtNOS). The first two isoforms are reported to be expressed in mouse follicles, oocytes, and pre-implantation embryos (Nishikimi A et al. 2001 Reproduction 122, 957–963). However, the role of any of these isoforms have not yet been investigated in bovine embryos. Here we aimed to examine the role of NOS in in vitro development of bovine embryos by treating embryos with NOS inhibitor, N-omega-L-nitro-arginine methyl esther (L-NAME), and examining the localization of the protein in pre-implantation embryos. Oocytes and embryos were grown in the media with NOS inhibitor added at a level of 0 mM (control), 1 mM, and 10 mM to either maturation or culture medium. Each experiment was conducted in four replicates each containing 100 oocytes for IVP. Cleavage and blastocyst rate were recorded at Days 2 and 7, respectively. Data were analyzed using the General Linear Model in SAS version 8.02 (SAS Institute, Inc., Cary, NC, USA) with the main factors being the level of L-NAME and the point of application. Pairwise comparisons were done using the Tukey test. Protein localization in bovine oocytes and embryos was performed by immunocytochemistry using eNOS- and iNOS-specific antibodies. Embryos were fixed in 3.7% paraformaldehyde, permeabilized in 0.1% Triton-X100, and washed three times in PBS supplemented with BSA. They were incubated with eNOS and iNOS primary antibody (1:200 dilutions) and washed before incubation with secondary antibody conjugated to FITC. After washing they were mounted on glass slides and examined under a confocal laser scanning microscope (Carl Zeiss Jena, Carl Zeiss AG, Oberkochen, Germany). In the controls the primary antibodies were omitted. As shown in the table below, the presence of L-NAME in the maturation medium significantly reduced the cleavage and blastocyst rate independent of the dosage applied. However the presence of L-NAME in the culture medium had an influence only on the blastocyst rate. The immunocytochemical staining results showed that both eNOS and iNOS are expressed in the cytoplasm of the MII oocytes, and during the pre-implantation stage the fluorescence signal was observed in nuclei and cytoplasm. However, the nuclear signal was much weaker. In conclusion, the present study is the first to determine the role of NO and to detect NOS protein in bovine oocytes and pre-implantation embryos. These results indicate that nitric oxide may play an important role as diffusible regulator of bovine oocyte maturation and preimplantation embryo development. Table 1. Effect of l-name addition in maturation or culture medium on embryo development

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