scholarly journals Dietary Nitrite: from menace to marvel

2016 ◽  
Vol 6 (11) ◽  
pp. 691 ◽  
Author(s):  
Nathan S. Bryan
Keyword(s):  
Nitric Oxide ◽  
Health Benefits ◽  
Biomedical Science ◽  
No Production ◽  
Positive Health ◽  
Therapeutic Benefits ◽  
Rigorous Research ◽  
Science Community ◽  
Nitrite Nitrate ◽  
Nutrition Epidemiology

Background: There are now indisputable health benefits of nitrite when administered in a clinical setting for specific diseases.  Most of the published reports identify the production of nitric oxide (NO) as the mechanism of action for nitrite.  Basic science as well as clinical studies demonstrates nitrite and/or nitrate can restore NO homeostasis as an endothelium independent source of NO that may be a redundant system for endogenous NO production.  Nitrate must first be reduced to nitrite by oral commensal bacteria and then nitrite further reduced to NO along the physiological oxygen gradient.  Despite decades of rigorous research on its safety and efficacy as a curing agent, sodium nitrite is still regarded by many as a toxic undesirable food additive.  However, research within the biomedical science community has revealed enormous therapeutic benefits of nitrite that is currently being developed as novel therapies for conditions associated with nitric oxide insufficiency.  This review will highlight the fundamental biochemistry of nitrite and nitrate in human physiology and provide evidence that nitrite and nitrate be considered essential nutrients.  Foods or diets enriched with nitrite can have profound positive health benefits. Keywords: nitrite, nitrate, nitric oxide, curing, nutrition, epidemiology, cardiovascular, cancer, diet, nitrosamines, antioxidants

scholarly journals Cholesterol induces renal vasoconstriction and anti-natriuresis by inhibiting nitric oxide production in anesthetized rats

2009 ◽  
Vol 297 (6) ◽  
pp. F1606-F1613 ◽  
Author(s):  
Libor Kopkan ◽  
Md Abdul H. Khan ◽  
Agnieszka Lis ◽  
Mouhamed S. Awayda ◽  
Dewan S. A. Majid
Keyword(s):  
Nitric Oxide ◽  
Sodium Reabsorption ◽  
No Production ◽  
Sprague Dawley ◽  
Appreciable Change ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Renal Responses

Although hypercholesterolemia is implicated in the pathophysiology of many renal disorders as well as hypertension, its direct actions in the kidney are not yet clearly understood. In the present study, we evaluated renal responses to administration of cholesterol (8 μg·min−1·100 g body wt−1; bound by polyethylene glycol) into the renal artery of anesthetized male Sprague-Dawley rats. Total renal blood flow (RBF) was measured by a Transonic flow probe, and glomerular filtration rate (GFR) was determined by Inulin clearance. In control rats ( n = 8), cholesterol induced reductions of 10 ± 2% in RBF [baseline (b) 7.6 ± 0.3 μg·min−1·100 g−1], 17 ± 3% in urine flow (b, 10.6 ± 0.9 μg·min−1·100 g−1), 29 ± 3% in sodium excretion (b, 0.96 ± 0.05 μmol·min−1·100 g−1) and 24 ± 2% in nitrite/nitrate excretion (b, 0.22 ± 0.01 nmol·min−1·100 g−1) without an appreciable change in GFR (b, 0.87 ± 0.03 ml·min−1·100 g−1). These renal vasoconstrictor and anti-natriuretic responses to cholesterol were absent in rats pretreated with nitric oxide (NO) synthase inhibitor, nitro-l-arginine methylester (0.5 μg·min−1·100 g−1; n = 6). In rats pretreated with superoxide (O2−) scavenger tempol (50 μg·min−1·100 g−1; n = 6), the cholesterol-induced renal responses remained mostly unchanged, although there was a slight attenuation in anti-natriuretic response. This anti-natriuretic response to cholesterol was abolished in furosemide-pretreated rats (0.3 μg·min−1·100 g−1; n = 6) but remained unchanged in amiloride-pretreated rats (0.2 μg·min−1·100 g−1; n = 5), indicating that Na+/K+/2Cl− cotransport is the dominant mediator of this effect. These data demonstrate that cholesterol-induced acute renal vasoconstrictor and antinatriuretic responses are mediated by a decrease in NO production. These data also indicate that tubular effect of cholesterol on sodium reabsorption is mediated by the furosemide sensitive Na+/K+/2Cl− cotransporter.

scholarly journals Anti-Hypertensive Activity of Novel Peptides Identified from Olive Flounder (Paralichthys olivaceus) Surimi

Foods ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 647
Author(s):  
Jae-Young Oh ◽  
Jun-Geon Je ◽  
Hyo-Geun Lee ◽  
Eun-A Kim ◽  
Sang In Kang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Umbilical Vein ◽  
Paralichthys Olivaceus ◽  
Health Benefits ◽  
Olive Flounder ◽  
Antihypertensive Activity ◽  
No Production ◽  
Food Ingredient ◽  
Food Ingredients ◽  
Olive Flounder Paralichthys Olivaceus

There is a growing interest in the health benefits of functional foods. A benefit that has been long sought is the control of hypertension through dietary approaches. Hypertension has been implicated as a risk factor for cardiovascular disease and is therefore of clinical significance. Here, we aim to demonstrate the antihypertensive activity of novel peptides derived from surimi, a functional food ingredient made from refined fish myofibrillar proteins. Three peptides, Ile-Val-Asp-Arg (IVDR), Trp-Tyr-Lys (WYK), and Val-Ala-Ser-Val-Ile (VASVI), were isolated from surimi made from the olive flounder (Paralichthys olivaceus). Our results show that IVDR, WYK, and VASVI exhibited high Angiotensin I-converting Enzyme (ACE) inhibition activity. These peptides are also shown to increase phosphorylation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS), and significantly promote nitric oxide (NO) production in human umbilical vein endothelial cells. Oral administration of the peptides decreased blood pressure in spontaneously hypertensive rats (SHRs), thereby confirming that the peptides derived from surimi perform antihypertensive activity via the Akt/eNOS pathway. These results indicate that surimi made from P. olivaceus contains novel antihypertensive peptides that could be used to enhance the health benefits of food ingredients.

Nitric oxide synthesis by rat pleural mesothelial cells: induction by cytokines and lipopolysaccharide

1993 ◽  
Vol 265 (2) ◽  
pp. L110-L116 ◽  
Author(s):  
M. W. Owens ◽  
M. B. Grisham
Keyword(s):  
Nitric Oxide ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
No Production ◽  
Nitrate Accumulation ◽  
Pleural Mesothelial Cells ◽  
Nitrate Production ◽  
Close Proximity ◽  
Nitrite Nitrate

The close proximity of pleural mesothelial cells (PMC) and mononuclear cells during pleural inflammation suggests that leukocyte-derived products (e.g., cytokines) may play an important role in modulating PMC function. The purpose of this study was to determine whether certain cytokines and bacterial products induce PMC to produce nitric oxide (NO). Confluent monolayers of rat PMC were exposed to tumor necrosis factor (TNF), interleukin-1 beta (IL-1), gamma-interferon (IFN), or lipopolysaccharide (LPS) individually and in various double and triple combinations for 6–72 h. Concentrations of nitrite and nitrate were quantified and used as indirect indices of NO production. Nitrite/nitrate accumulation was maximal at 72 h, with most of the increase occurring from 48 to 72 h. Maximal nitrite/nitrate production was observed with triple combinations with the combination of LPS, IL-1, and TNF giving the highest concentration (137.4 +/- 2.8 microM). Nitrite/nitrate production was significantly inhibited by NG-nitro-L-arginine methyl ester, suggesting that nitrite and nitrate were derived from the L-arginine-dependent formation of NO. These data indicate that PMC can be induced to produce large amounts of NO in response to specific combinations of proinflammatory cytokines and LPS.

Role of nitric oxide in airway remodelling

2000 ◽  
Vol 98 (3) ◽  
pp. 291-294 ◽  
Author(s):  
Esteban C. GABAZZA ◽  
Osamu TAGUCHI ◽  
Shigenori TAMAKI ◽  
Shuichi MURASHIMA ◽  
Hiroyasu KOBAYASHI ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Causative Factor ◽  
Wall Thickening ◽  
No Production ◽  
Airway Remodelling ◽  
Pathophysiological Mechanism ◽  
Airway Wall ◽  
High Resolution Computed Tomography ◽  
Bronchial Wall ◽  
Nitrite Nitrate

Airway remodelling, which is manifested by thickening of bronchial wall, is an important causative factor of bronchial hyper-responsiveness in asthma. The pathophysiological mechanism of airway remodelling is not clear. In the present study we evaluated the relationship between nitric oxide (NO) generation and airway wall thickening in patients with chronic asthma. As a marker of NO production, the levels of nitrite/nitrate were measured in induced sputum, and bronchial wall thickening was measured by high-resolution computed tomography. Sputum concentrations of nitrite/nitrate were significantly increased in asthmatic patients compared with controls. The ratio of airway wall thickness to lumen diameter was significantly correlated with the sputum concentration of nitrite/nitrate. Although statistical correlation does not prove causation, this finding suggests that NO may play a key role in the pathogenesis of airway remodelling.

scholarly journals Pharmacological characterisation of arthritis induced byBothrops jararacavenom in rabbits: a positive cross talk between bradykinin, nitric oxide and prostaglandin E2

2002 ◽  
Vol 11 (1) ◽  
pp. 13-16 ◽  
Author(s):  
Suzana B. V. Mello ◽  
Maria Luiza Guzzo ◽  
Luiz Filipe Santiago Lisboa ◽  
Sandra H. P. Farsky
Keyword(s):  
Nitric Oxide ◽  
Prostaglandin E ◽  
No Production ◽  
Positive Interaction ◽  
Kinin System ◽  
Local Inflammatory Response ◽  
Griess Reaction ◽  
Hoe 140 ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor

Background: Our previous results showed that nitric oxide (NO) and bradykinin (BK) mediate the arthritis induced byBothrops jararacavenom (BjV) in rabbits. In this study, we investigated the contribution of each receptor of BK as well as the inter-relationship between NO and eicosanoids in BjV-induced arthritis.Methods: The arthritis was induced in rabbits with 16 μg of BjV injected intra-articularly. Prostaglandin E2(PGE2), thromboxane B2(TxB2), leukotriene B4(LTB4) (radioimmunoassay) and nitrite/nitrate concentrations (NO2/NO3) (Griess reaction) were evaluated in the synovial fluid 4 h later. The animals were prior treated with NO synthase inhibitor (L-NAME; 20 mg/kg/day for 14 days), the B2 antagonist of BK (HOE-140) and the B1 antagonist of BK (des-Arg9[Leu8]-bradykinin), both at a dose of 0.3 mg/kg, 30 min prior to the venom injection.Results: Data show that L-NAME and HOE-140 treatment were equally able to reduce PGE2and NO2/NO3levels without interfering with TxB2and LTB4production. On the contrary, the B1 antagonist of BK inhibited TxB2and LTB4production, and did not alter PGE2and NO metabolites levels in the inflamed joint.Discussions: The results presented clarify the contribution of the kinin system, mainly through the B2 receptor, to the local inflammatory response induced by BjV, as well as its positive interaction with PGE2and NO production.

scholarly journals Glycyrrhizin as a Nitric Oxide Regulator in Cancer Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5762
Author(s):  
Minsu Kim ◽  
Seok Chan Park ◽  
Dong Yun Lee
Keyword(s):  
Nitric Oxide ◽  
Multidrug Resistance ◽  
Tumor Microenvironment ◽  
Cancer Chemotherapy ◽  
Active Compound ◽  
Potential Role ◽  
No Production ◽  
Therapeutic Benefits ◽  
And Function

Chemotherapy is used widely for cancer treatment; however, the evolution of multidrug resistance (MDR) in many patients limits the therapeutic benefits of chemotherapy. It is important to overcome MDR for enhanced chemotherapy. ATP-dependent efflux of drugs out of cells is the main mechanism of MDR. Recent studies have suggested that nitric oxide (NO) can be used to overcome MDR by inhibiting the ATPase function of ATP-dependent pumps. Several attempts have been made to deliver NO to the tumor microenvironment (TME), however there are limitations in delivery. Glycyrrhizin (GL), an active compound of licorice, has been reported to both reduce the MDR effect by inhibiting ATP-dependent pumps and function as a regulator of NO production in the TME. In this review, we describe the potential role of GL as an NO regulator and MDR inhibitor that efficiently reduces the MDR effect in cancer chemotherapy.

scholarly journals Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis

2001 ◽  
Vol 280 (6) ◽  
pp. H2848-H2856 ◽  
Author(s):  
Ryon M. Bateman ◽  
Justin E. Jagger ◽  
Michael D. Sharpe ◽  
Mary L. Ellsworth ◽  
Sanjay Mehta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Cecal Ligation ◽  
Capillary Density ◽  
Erythrocyte Deformability ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Nitrite Nitrate ◽  
Plasma Nitrite ◽  
Rbc Deformability

Erythrocyte deformability has been recognized as a determinant of microvascular perfusion. Because nitric oxide (NO) is implicated in the modulation of red blood cell (RBC) deformability and NO levels increase during sepsis, we tested the hypothesis that a NO-mediated decrease in RBC deformability contributes to decreased functional capillary density (CD) in remote organs. With the use of a peritonitis model of sepsis in the rat [cecal ligation and perforation (CLP)] and aminoguanidine (AG) to prevent increases in NO, we measured CD in skeletal muscle (intravital microscopy), mean erythrocyte membrane deformability ([Formula: see text]; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NOx) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NOx increased 254% ( P < 0.05), stopped flow capillaries increased 149% ( P < 0.05), and [Formula: see text] decreased 12.7% ( P < 0.05), with a subpopulation (5%) of RBC with deformabilities below the normal range. AG prevented increases in NOx, accumulation of HbNO, and decreases in both [Formula: see text]and functional CD. We found no evidence of leukocyte plugging postcapillary venules. Our findings suggest that decreased functional CD during sepsis resulted from a NO-mediated decrease in erythrocyte deformability.

scholarly journals Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1184-1195 ◽  
Author(s):  
JB Weinberg ◽  
MA Misukonis ◽  
PJ Shami ◽  
SN Mason ◽  
DL Sauls ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocytes ◽  
Inos Mrna ◽  
No Production ◽  
Human Monocytes ◽  
Low Levels ◽  
Nitrite Nitrate ◽  
Oxide Synthase

Abstract Nitric oxide (NO) is produced by numerous different cell types, and it is an important regulator and mediator of many processes including smooth muscle relaxation, neurotransmission, and murine macrophage- mediated cytotoxicity for microbes and tumor cells. Although murine macrophages produce NO readily after activation, human monocytes and tissue macrophages have been reported to produce only low levels of NO in vitro. The purpose of this study was to determine if stimulated human mononuclear phagocytes produce inducible nitric oxide synthase (iNOS) mRNA, protein, and enzymatic activity. By reverse transcriptase- polymerase chain reaction (RT-PCR) analysis, we show that human monocytes can be induced to express iNOS mRNA after treatment with lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma). By immunofluorescence and immunoblot analyses, we show monocytes and peritoneal macrophages contain detectable levels of iNOS antigen after stimulations with cytokines in vitro. Control monocytes or those cultured with LPS and/or various cytokines have low levels of NOS functional activity as measured by the ability of cell extracts to convert L-arginine to L-citrulline, and they produce low levels of the NO catabolites nitrite and nitrate. Peritoneal macrophages have significantly enhanced nitrite/nitrate production and NOS activity after treatment with LPS and/or IFN-gamma, whereas monocyte nitrite/nitrate production and NOS activity are not altered by the treatments. Monocytes cultured with various live or heat-killed bacteria, fungi, or human immunodeficiency virus (HIV)-1 do not produce high levels of nitrite/nitrate. Antibodies against transforming growth factor-beta (TGF-beta), a factor known to inhibit iNOS expression and NO production in mouse macrophages, do not enhance NO production in human monocytes or macrophages. Biopterin, an obligate cofactor of iNOS enzymatic activity, is undetectable in freshly isolated or cultured human monocytes and peritoneal macrophages. However, replenishment of intracellular levels of tetrahydrobiopterin by culture with the cell- permeable, nontoxic precursor sepiapterin does not enhance the abilities of the human mononuclear phagocytes to produce NO in vitro. Mixing experiments show no evidence of a functional NOS inhibitor in human mononuclear phagocytes. Thus, we demonstrate that human mononuclear phagocytes can produce iNOS mRNA and protein, and (despite this) their abilities to generate NO are very low.

scholarly journals L-Citrulline Supplementation Increases Plasma Nitric Oxide Levels and Reduces Arginase Activity in Patients With Type 2 Diabetes

2020 ◽  
Vol 11 ◽  
Author(s):  
Alia Shatanawi ◽  
Munther S. Momani ◽  
Ruaa Al-Aqtash ◽  
Mohammad H Hamdan ◽  
Munir N. Gharaibeh
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Endothelial Cells ◽  
Vascular Dysfunction ◽  
Arginase Activity ◽  
Diabetic Patients ◽  
No Production ◽  
Major Contributor ◽  
Therapeutic Benefits

Type 2 diabetes mellitus (T2DM) is becoming a major contributor to cardiovascular disease. One of the early signs of T2DM associated cardiovascular events is the development of vascular dysfunction. This dysfunction has been implicated in increasing the morbidity and mortality of T2DM patients. One of the important characteristics of vascular dysfunction is the impaired ability of endothelial cells to produce nitric oxide (NO). Additionally, decreases in the availability of NO is also a major contributor of this pathology. NO is produced by the activity of endothelial NO synthase (eNOS) on its substrate, L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence, increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. Diabetes has been linked to elevated arginase and associated vascular endothelial dysfunction. We aimed to determine levels of plasma NO and arginase activity in (T2DM) patients and the effects of L-citrulline supplementation, a natural arginase inhibitor, on inhibiting arginase activity in these patients. Levels of arginase correlated with HbA1c levels in diabetic patients. Twenty-five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity decreased by 21% in T2DM patients after taking L-citrulline supplements. Additionally, plasma NO levels increased by 38%. There was a modest improvement on H1Ac levels in these patients, though not statistically significant. The effect of L-citrulline on arginase activity was also studied in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25 mM, 72 h) caused a 2-fold increase in arginase activity in BAECs and decreased NO production by 30%. L-citrulline (2.5 mM) completely prevented the increase in arginase activity and restored NO production levels. These data indicate that L-citrulline can have therapeutic benefits in diabetic patients through increasing NO levels and thus maintaining vascular function possibly through an arginase inhibition related pathway.

scholarly journals Prolactin alters blood pressure by modulating the activity of endothelial nitric oxide synthase

2016 ◽  
Vol 113 (44) ◽  
pp. 12538-12543 ◽  
Author(s):  
Albert S. Chang ◽  
Ruriko Grant ◽  
Hirofumi Tomita ◽  
Hyung-Suk Kim ◽  
Oliver Smithies ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Function ◽  
Single Copy ◽  
No Production ◽  
Plasma Prolactin ◽  
Cytochrome P450 1A1 ◽  
Normal Chow ◽  
Nitrite Nitrate ◽  
Endothelial Nitric Oxide

Increased levels of a cleaved form of prolactin (molecular weight 16 kDa) have been associated with preeclampsia. To study the effects of prolactin on blood pressure (BP), we generated male mice with a single-copy transgene (Tg; inserted into the hypoxanthine-guanine phosphoribosyltransferase locus) that enables inducible hepatic production of prolactin and its cleavage product. The Tg is driven by the indole-3-carbinol (I3C)-inducible rat cytochrome P450 1A1 promoter. When the Tg mice were fed normal chow (NC), plasma prolactin concentrations were comparable to those in female WT mice in the last third of pregnancy, and BP was lower than in WT mice (∼95 mm Hg vs. ∼105 mm Hg). When the Tg mice were fed chow containing IC3, plasma prolactin concentrations increased threefold, BP increased to ∼130 mm Hg, and cardiac function became markedly impaired. IC3 chow did not affect the WT mice. Urinary excretion of nitrite/nitrate and the amount of Ser1177-phosphorylated endothelial nitric oxide (NO) synthase (eNOS) were significantly greater in the Tg mice fed NC than in WT mice, as they are during pregnancy. However, when I3C was fed, these indicators of NO production became significantly less in the Tg mice than in WT mice. The effects of increased plasma prolactin were abolished by a genetic absence of eNOS. Thus, a threefold increase in plasma prolactin is sufficient to increase BP significantly and to markedly impair cardiac function, with effects mediated by NO produced by eNOS. We suggest that pregnant women with abnormally high prolactin levels may need special attention.

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