scholarly journals I. Physiological chemistry of nitric oxide and its metabolites: implications in inflammation

1999 ◽  
Vol 276 (2) ◽  
pp. G315-G321 ◽  
Author(s):  
Matthew B. Grisham ◽  
David Jourd’Heuil ◽  
David A. Wink
Keyword(s):  
Nitric Oxide ◽  
Indirect Effects ◽  
Tissue Injury ◽  
No Production ◽  
Physiological Chemistry ◽  
Reactive Nitrogen Oxide Species ◽  
Anti Inflammatory ◽  
The Many ◽  
Active Inflammation

The role of nitric oxide (NO) in inflammation represents one of the most studied yet controversial subjects in physiology. A number of reports have demonstrated that NO possesses potent anti-inflammatory properties, whereas an equally impressive number of studies suggest that NO may promote inflammation-induced cell and tissue dysfunction. The reasons for these apparent paradoxical observations are not entirely clear; however, we propose that understanding the physiological chemistry of NO and its metabolites will provide a blueprint by which one may distinguish the regulatory/anti-inflammatory properties of NO from its deleterious/proinflammatory effects. The physiological chemistry of NO is complex and encompasses numerous potential reactions. In an attempt to simplify the understanding of this chemistry, the physiological aspects of NO chemistry may be categorized into direct and indirect effects. This type of classification allows for consideration of timing, location, and rate of production of NO and the relevant targets likely to be affected. Direct effects are those reactions in which NO interacts directly with a biological molecule or target and are thought to occur under normal physiological conditions when the rates of NO production are low. Generally, these types of reactions may serve regulatory and/or anti-inflammatory functions. Indirect effects, on the other hand, are those reactions mediated by NO-derived intermediates such as reactive nitrogen oxide species derived from the reaction of NO with oxygen or superoxide and are produced when fluxes of NO are enhanced. We postulate that these types of reactions may predominate during times of active inflammation. Consideration of the physiological chemistry of NO and its metabolites will hopefully allow one to identify which of the many NO-dependent reactions are important in modulating the inflammatory response and may help in the design of new therapeutic strategies for the treatment of inflammatory tissue injury.

III. A molecular prelude to intestinal inflammation

1999 ◽  
Vol 276 (4) ◽  
pp. G795-G799 ◽  
Author(s):  
Mark J. S. Miller ◽  
Manuel Sandoval
Keyword(s):  
Nitric Oxide ◽  
Nitrogen Oxides ◽  
Chronic Inflammation ◽  
Intestinal Inflammation ◽  
Tissue Injury ◽  
Direct Interaction ◽  
Oxides Of Nitrogen ◽  
Anti Inflammatory ◽  
Oxide Synthase

Nitric oxide (NO) synthesis is markedly augmented in states of inflammation, largely due to the expression of inducible nitric oxide synthase (iNOS). Although NO has anti-inflammatory consequences under basal conditions, it remains enigmatic as to why NO displays proinflammatory characteristics in chronic inflammation. Either the anti-inflammatory actions are weak and of little consequence or, alternatively, other factors influence the role of NO in chronic inflammation. We propose that the answer to this enigma lies in the conversion of NO to other higher oxides of nitrogen (NO2, nitrogen dioxide; N2O3, dinitrogen trioxide; and ONOO−, peroxynitrite). Emerging therapeutic strategies may be independent of NO synthesis; e.g., antioxidants have no direct interaction with NO but attenuate the levels and activity of higher nitrogen oxides. Thus, whereas iNOS may be a marker for the proinflammatory actions of NO, the species that mediate tissue injury/dysfunction in inflammation are likely to be nitrogen oxides other than NO.

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.

Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases

2005 ◽  
Vol 289 (6) ◽  
pp. F1324-F1332 ◽  
Author(s):  
Manish M. Tiwari ◽  
Robert W. Brock ◽  
Judit K. Megyesi ◽  
Gur P. Kaushal ◽  
Philip R. Mayeux
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Blood Flow ◽  
Saline Group ◽  
No Production ◽  
Capillary Perfusion ◽  
Peritubular Capillary ◽  
Synthase Inhibitor ◽  
Peritubular Capillary Perfusion

Acute renal failure (ARF) is a frequent and serious complication of endotoxemia caused by lipopolysaccharide (LPS) and contributes significantly to mortality. The present studies were undertaken to examine the roles of nitric oxide (NO) and caspase activation on renal peritubular blood flow and apoptosis in a murine model of LPS-induced ARF. Male C57BL/6 mice treated with LPS ( Escherichia coli) at a dose of 10 mg/kg developed ARF at 18 h. Renal failure was associated with a significant decrease in peritubular capillary perfusion. Vessels with no flow increased from 7 ± 3% in the saline group to 30 ± 4% in the LPS group ( P < 0.01). Both the inducible NO synthase inhibitor l- N6-1-iminoethyl-lysine (l-NIL) and the nonselective caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD) prevented renal failure and reversed perfusion deficits. Renal failure was also associated with an increase in renal caspase-3 activity and an increase in renal apoptosis. Both l-NIL and Z-VAD prevented these changes. LPS caused an increase in NO production that was blocked by l-NIL but not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal caspases and the resulting disruption in peritubular blood flow are an important mechanism of LPS-induced ARF.

Nitrate reductases and hemoglobins control nitrogen-fixing symbiosis by regulating nitric oxide accumulation

2020 ◽  
Author(s):  
Antoine Berger ◽  
Alexandre Boscari ◽  
Alain Puppo ◽  
Renaud Brouquisse
Keyword(s):  
Nitric Oxide ◽  
Defense Responses ◽  
Nodule Formation ◽  
No Production ◽  
Degradation Pathways ◽  
Atmospheric Nitrogen ◽  
Metabolic Intermediate ◽  
Hypoxic Environment ◽  
Nitrate Reductases

Abstract The interaction between legumes and rhizobia leads to the establishment of a symbiotic relationship between plant and bacteria. This is characterized by the formation of a new organ, the nodule, which facilitates the fixation of atmospheric nitrogen (N2) by nitrogenase through the creation of a hypoxic environment. Nitric oxide (NO) accumulates at each stage of the symbiotic process. NO is involved in defense responses, nodule organogenesis and development, nitrogen fixation metabolism, and senescence induction. During symbiosis, either successively or simultaneously, NO regulates gene expression, modulates enzyme activities, and acts as a metabolic intermediate in energy regeneration processes via phytoglobin-NO respiration and the bacterial denitrification pathway. Due to the transition from normoxia to hypoxia during nodule formation, and the progressive presence of the bacterial partner in the growing nodules, NO production and degradation pathways change during the symbiotic process. This review analyzes the different source and degradation pathways of NO, and highlights the role of nitrate reductases and hemoproteins of both the plant and bacterial partners in the control of NO accumulation.

scholarly journals Recent insights into nitrite signaling processes in blood

2017 ◽  
Vol 398 (3) ◽  
pp. 319-329 ◽  
Author(s):  
Christine C. Helms ◽  
Xiaohua Liu ◽  
Daniel B. Kim-Shapiro
Keyword(s):  
Nitric Oxide ◽  
Human Physiology ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Nitrite Reduction ◽  
No Production ◽  
The Past ◽  
Acidic Conditions ◽  
Hypoxic Vasodilation

Abstract Nitrite was once thought to be inert in human physiology. However, research over the past few decades has established a link between nitrite and the production of nitric oxide (NO) that is potentiated under hypoxic and acidic conditions. Under this new role nitrite acts as a storage pool for bioavailable NO. The NO so produced is likely to play important roles in decreasing platelet activation, contributing to hypoxic vasodilation and minimizing blood-cell adhesion to endothelial cells. Researchers have proposed multiple mechanisms for nitrite reduction in the blood. However, NO production in blood must somehow overcome rapid scavenging by hemoglobin in order to be effective. Here we review the role of red blood cell hemoglobin in the reduction of nitrite and present recent research into mechanisms that may allow nitric oxide and other reactive nitrogen signaling species to escape the red blood cell.

scholarly journals Anti-Inflammatory Activity of Populus deltoides Leaf Extract via Modulating NF-κB and p38/JNK Pathways

2018 ◽  
Vol 19 (12) ◽  
pp. 3746 ◽  
Author(s):  
Ye Jeong ◽  
Mi-Young Lee
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Leaf Extract ◽  
Populus Deltoides ◽  
Nuclear Translocation ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Activity ◽  
No Production ◽  
Anti Inflammatory

Populus deltoides, known as eastern cottonwood, has been commonly used as a medicinal plant. The aim of the present study was to investigate the mechanism underlying the anti-inflammatory activity of P. deltoides leaf extract (PLE). PLE effectively inhibited the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, but not that of cyclooxygenase-2 (COX-2) and prostaglandin E2. Proinflammatory tumor necrosis factor alpha (TNF-α) levels were also reduced by the extract. PLE inhibited the phosphorylation of nuclear factor-kappa B (NF-κB) and inhibitor of Kappa Bα (IκBα), and blunted LPS-triggered enhanced nuclear translocation of NF-κB p65. In mitogen-activated protein kinase (MAPK) signaling, PLE effectively decreased the phosphorylation of p38 and c-Jun N-terminal protein kinase (JNK), but not of extracellular signal-regulated kinase 1/2 (ERK1/2). Taken together, these results suggest that anti-inflammatory activity of P. deltoides leaf extract might be driven by iNOS and NO inhibition mediated by modulation of the NF-κB and p38/JNK signaling pathways.

Losartan Increases No Production from the Bovine Aortic Wall That is Stimulated by Angiotensin II

2003 ◽  
Vol 1 (3) ◽  
pp. 113-117 ◽  
Author(s):  
M. Myronidou ◽  
B. Kokkas ◽  
A. Kouyoumtzis ◽  
N. Gregoriadis ◽  
A. Lourbopoulos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Aortic Wall ◽  
Vascular Wall ◽  
Protective Role ◽  
Normal Function ◽  
No Production ◽  
Chemical Inactivation

In these studies we investigated if losartan, an AT1- receptor blocker has any beneficial effect on NO production from the bovine aortic preparations in vitro while under stimulation from angiotensin II. Experiments were performed on intact specimens of bovine thoracic aorta, incubated in Dulbeco's MOD medium in a metabolic shaker for 24 hours under 95 % O2 and 5 % CO2 at a temperature of 37°C. We found that angiotensin II 1nM−10 μM does not exert any statistically significant action on NO production. On the contrary, angiotensin II 10nM increases the production of NO by 58.14 % (from 12.16 + 2.9 μm/l to 19.23 + 4.2 μm/l in the presence of losartan 1nM (P<0.05). Nitric oxide levels depend on both rate production and rate catabolism or chemical inactivation. Such an equilibrium is vital for the normal function of many systems including the cardiovascular one. The above results demonstrate that the blockade of AT1-receptors favors the biosynthesis of NO and indicate the protective role of losartan on the vascular wall.

scholarly journals Anti-Inflammatory Activity of Extract Mixture of Annona senegalensis Pers. and Piliostigma thonningii (Schum.)

2020 ◽  
Vol 10 (6-s) ◽  
pp. 103-108
Author(s):  
Komlatsè Togbenou ◽  
Kokou Idoh ◽  
Kossivi Dosseh ◽  
Tchazou Kpatcha ◽  
Amégnona Agbonon
Keyword(s):  
Nitric Oxide ◽  
Ethanolic Extract ◽  
No Production ◽  
Leukocyte Infiltration ◽  
Inflammation Markers ◽  
Asthma Model ◽  
Piliostigma Thonningii ◽  
Anti Inflammatory ◽  
Inflammatory Component ◽  
Inflammatory Effect

Introduction: Annona senegalensis Pers (Annonaceae) and Piliostigma thonningii (Schum.) (Leguminoseae)  are two medicinal plants used, often in combination, in traditional Togolese medicine for the treatment of diseases with an inflammatory component. Objective: The aim of this study is to evaluate the anti-inflammatory effect of the hydro-ethanolic extract (EHEM) of the combination of A. senegalensis and P. thonningii (1: 1, m: m). Methods: The ovalbumin-induced allergic airway asthma model was used. Animals made asthmatic were treated with EHEM at doses of 250 and 500 mg / kg. Inflammation markers including histamine, nitric oxide (NO), vascular leakage, leukocyte infiltration in the airways, and malondialdehyde (MDA), were measured. Results: Compared to the SNT group, EHEM inhibits the infiltration of the airways by leukocytes (850,00 × 103 ± 50 cells / mL vs 1830 × 103 ± 53,85 cells / mL for ST500 mg / kg, P <0,05). It inhibited vascular permeability to Evans Blue (10,40 ± 0,270 μg / mL vs ST500, p<0,05). It inhibited histamine release (13,95 ± 0,937 μg / mL vs 32,78 ± 1,044 μg / mL, p<0,05) and NO production (0,211 ± 0,008 Μm vs 0,315 ± 0,022 μM, p<0,05). It finally inhibited MDA production (14,66 ± 0,533 nM / mL vs 9,014 ± 0,366 nM / mL and 7,149 ± 0,300 nM / mL, p<0,05) in lung tissue. Conclusion: Our results suggest that EHEM inhibits OVA-induced inflammation. These results justify the use of this combination of plants in traditional Togolese medicine. Keywords: Inflammation, malondialdehyde, Annona senegalensis, Piliostigma thonningii.

Abstract 153: Bile Acid Receptor TGR5 Agonism Represents Anti-inflammatory Effects via Stimulating Nitric Oxide Production in Vascular Endothelial Cells

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Taiki Kida ◽  
Yoshiki Tsubosaka ◽  
Masatoshi Hori ◽  
Hiroshi Ozaki ◽  
Takahisa Murata
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Bile Acids ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Lithocholic Acid ◽  
Signal Pathways ◽  
No Production ◽  
Vascular Endothelial ◽  
Anti Inflammatory

Objective TGR5, a membrane-bound, G-protein-coupled receptor for bile acids, is known to be involved in regulation of energy homeostasis and inflammation. However, little is known about the function of TGR5 in vascular endothelial cells. In the present study, we examined whether TGR5 agonism represents anti-inflammatory effects in vascular endothelial cells focusing on nitric oxide (NO) production. Methods and Results In human umbilical vein endothelial cells (HUVECs), treatment with taurolithocholic acid (TLCA), which has the highest affinity to TGR5 among various bile acids, significantly reduced tumor necrosis factor (TNF)-α-induced vascular cell adhesion molecule (VCAM)-1 protein expression and adhesion of human monocytes, U937. These effects were abrogated by a NO synthase (NOS) inhibitor, N G -Monomethyl-L-arginine (L-NMMA). In bovine aortic endothelial cells (BAECs), treatment with TLCA as well as lithocholic acid, which also has high affinity to TGR5, significantly increased the NO production. In contrast, deoxycholic acid and chenodeoxycholic acid, which possess low affinity to TGR5, did not affect the NO production. Gene depletion of TGR5 by siRNA transfection abolished TLCA-induced NO production in BAECs. TLCA-induced NO production was also observed in HUVECs measured as intracellular cGMP accumulation. We next investigated the signal pathways responsible for the TLCA-induced NO production in endothelial cells. Treatment with TLCA increased endothelial NOS (eNOS) ser1177 phosphorylation in HUVECs. This response was accompanied by increased Akt ser473 phosphorylation and intracellular Ca 2+ ([Ca 2+ ] i ). Treatment with phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or blockade of calcium channel with La 3+ , significantly decreased TLCA-induced eNOS ser1177 phosphorylation and subsequent NO production. Conclusion These results indicate that TGR5 agonism can mediate anti-inflammatory responses by suppressing VCAM-1 expression and monocytes adhesion to endothelial cells. This function is dependent on NO production via Akt activation and [Ca 2+ ] i increase.

V. Therapeutic potential of nitric oxide donors and inhibitors

1999 ◽  
Vol 276 (6) ◽  
pp. G1313-G1316 ◽  
Author(s):  
Marcelo N. Muscará ◽  
John L. Wallace
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Mucosal Injury ◽  
Therapeutic Agents ◽  
Gastrointestinal Physiology ◽  
Inflammatory Drugs ◽  
Nitric Oxide Releasing ◽  
Oxide Synthase

Nitric oxide is a crucial mediator of gastrointestinal mucosal defense, but, paradoxically, it also contributes to mucosal injury in several situations. Inhibitors of nitric oxide synthesis and compounds that release nitric oxide have been useful pharmacological tools for evaluating the role of nitric oxide in gastrointestinal physiology and pathophysiology. Newer inhibitors with selectivity for one of the isoforms of nitric oxide synthase are even more powerful tools and may have utility as therapeutic agents. Also, agents that can scavenge nitric oxide or peroxynitrite are promising as drugs to prevent nitric oxide-associated tissue injury. Compounds that release nitric oxide in small amounts over a prolonged period of time may also be very useful for prevention of gastrointestinal injury associated with shock and with the use of drugs that have ulcerogenic effects. Indeed, the coupling of a nitric oxide-releasing moiety to nonsteroidal anti-inflammatory drugs has proven to be a valid means of substantially reducing the gastrointestinal toxicity of these drugs without decreasing their efficacy.

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