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PubMed1985

Leukocyte esterase-nitrite and bioluminescence assays as urine screens.

The 1-min leukocyte esterase (LE)-nitrite test (Chemstrip 9; Biodynamics, Division of Boehringer Mannheim Biochemicals, Indianapolis, Ind.) and a bioluminescence assay (Monolight centrifugation method; Analytical Luminescence Laboratory, Inc., San Diego, Calif.) were tested for their efficacy as urine screens among 453 patients at a tertiary-care teaching hospital. Both methods had the capacity to exclude significant bacteriuria (greater than or equal to 10(5) CFU/ml) when compared with the results of conventional culture methods, with predictive values of 99 and 93%, respectively, for a negative test. Bioluminescence was the more accurate nonculture method used. Sensitivity and specificity values were 97 and 71%, respectively, for bioluminescence, 82 and 60%, respectively, for LE with nitrite, and 72 and 64%, respectively, for LE without nitrite. At reduced levels of bacteriuria less than 10(5) CFU/ml), the sensitivities of LE-nitrite and bioluminescence were decreased but comparable. The addition of protein and blood test results in the Chemstrip 9, along with LE-nitrite as bacteriuria indicators, were unsatisfactory because of the large numbers of false-positive results attributed to protein and blood determinations. LE activity as detected by the LE test was a poor predictor of significant bacteriuria in both male and female patients. The sensitivity (71%) and specificity (57%) of the LE test in male patients were significantly lower than those previously reported and varied with the patient population studied.

Bacteriuria↗

PubMed1987

Urinary nitrite in symptomatic and asymptomatic urinary infection.

The dipstrip test for urinary nitrite is fairly unreliable in symptomatic urinary infections and only 104 (52%) of 200 symptomatic children with urinary infection attending an emergency department had a positive result. The test yielded positive results, however, in 83 of 100 outpatients with largely asymptomatic urinary infection attending a follow up clinic because of known predisposition to urinary infection. This difference was highly significant. The finding of urinary nitrite is highly specific for urinary infection and only 1% of 300 uninfected urine specimens gave a positive result. After addition of a broth culture of Escherichia coli to sterile urine incubation at 37 degrees C for four to six hours was required before the nitrite test yielded positive results. This suggests that frequency of micturition in urinary infection reduces the reliability of the nitrite test. On the other hand, the use of overnight, first morning urine specimens may further improve the sensitivity. If nitrite testing is used for screening for urinary infection at home, however, patients should be warned not to rely on a negative result in the presence of symptoms of urinary infection.

Adolescent↗

PubMed1992

Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases.

Cytokines induce nitric oxide synthesis by endothelial cells, macrophages and polymorphonuclear leucocytes, indicating a role for nitric oxide in inflammatory processes. Nitric oxide production was therefore measured indirectly as nitrite in serum and synovial fluid samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) together with serum samples from healthy volunteers matched for age and sex. Serum nitrite concentrations in patients with RA and OA were significantly higher than in controls. In both disease groups synovial fluid nitrite was significantly higher than serum nitrite, implying nitric oxide synthesis by the synovium. Serum and synovial fluid nitrite concentrations in RA were also significantly higher than those in OA. These data show increased nitric oxide production in RA and OA and suggest a role for nitric oxide as an inflammatory mediator in rheumatic diseases.

Arthritis, Rheumatoid↗

PubMed1977

Nitrite and thiocyanate in the fasting and secreting stomach and in saliva.

The concentrations of nitrite and thiocyanate in fasting and pentagastrin stimulated gastric juice and in saliva have been examined. Nitrite was found in all of 17 samples of fasting gastric juice, mean 4-9 +/- 1-1 muM. Stimulation of gastric secretion with pentagastrin caused no significant change in nitrite concentration. Thiocyanate was detected in all of 21 samples of fasting gastric juice and the difference in concentration between smokers and non-smokers probably reflects similar differences in saliva. In contrast to the nitrite data there was a significant drop in thiocyanate concentration of gastric juice after pentagastrin from 0-9 +/- 0-1 mM to 0-3 +/- 0-04 mM, suggesting a salivary origin for the thiocyanate in gastric juice. Thiocyanate is a powerful catalyst of nitrosation, which, together with small amounts of nitrite and naturally occurring amines could lead to the intragastric formation of carcinogenic nitrosamines and in certain circumstances be a factor in the aetiology of gastric cancer.

Fasting↗

PubMed2000

Urinary nitrite excretion after prophylactic intravenous immunoglobulin in premature infants.

AIMS: To investigate the correlation between the prophylactic administration of intravenous immunoglobulin (IVIG) to preterm infants and urinary nitrite levels, which can be utilized as an index of endogenous nitric oxide (NO) formation, and to determine if NO formation plays a role in both therapeutic and adverse effects of IVIG. METHODS: 28 healthy preterm infants were included in this prospective study. They had a mean gestational age of 29.4 +/- 2.2 weeks and weight of 1,387 +/- 371 g. Prophylactic IVIG infusion at a dose of 0.5 g/kg/day was administered when they were 3-10 days old. Urine samples of the neonates were obtained for analysis on days 1, 2 and 3 after IVIG administration as well as 1 day before. Urinary nitrite levels obtained in the subjects were normalized for urinary creatinine concentrations. RESULTS: The mean urinary nitrite levels were: 2.77 +/- 1.66 micromol/mmol creatinine before IVIG administration; 4.33 +/- 3.88 micromol/mmol creatinine on the 1st day of IVIG; 3.77 +/- 2.73 micromol/mmol creatinine on the 2nd day, and 3.64 +/- 3.28 micromol/mmol creatinine on the 3rd day. There was a significant increase in urinary nitrite levels between before and after IVIG administration. There was no statistical difference in urinary nitrate levels between days 1, 2 and 3 after IVIG administration. CONCLUSION: We demonstrated that urinary nitrite excretion is significantly elevated in preterm infants after prophylactic IVIG administration and this result suggests that endogenous NO formation may play an important role in both the therapeutic and adverse effects of IVIG.

Birth Weight↗

PubMed1980

The exposure to humans to nitrite.

Although nitrate is more abundant than nitrite in food and the environment in general, it requires reduction by, for instance, bacterial or plant enzymes before it is involved in the nitrosation of amines or amides. Part of the exposure of humans to nitrite arises from its use as a food additive where it performs a very useful function in protecting the consumer from pathogenic micro-organisms such as Clostridium botulinum. Some untreated foodstuffs, such as potatoes, tomatoes and beets, also contain low levels of nitrite. Nevertheless, the main source of human contact is that produced in vivo from nitrate ingested in foods in general and in vegetables in particular. Nitrate also occurs widely in drinking water supplies and this source can also contribute in some measure to human exposure. As yet, it is not possible to compute with accuracy the contribution from any endogenous synthesis within the gastrointestinal tract. Since the rate of nitrosation of an amine is dependent on the nitrite concentration to a power of greater than unity, it is probable that nitrite ingested in one application over a short period will be more active in the synthesis of N-nitroso compounds than a continuous supply at lower concentrations over long periods.

Drinking↗

PubMed1997

Urinary nitrite excretion in low birth weight neonates with systemic inflammatory response syndrome.

Increased nitric oxide (NO) levels are thought to play an important role in the pathophysiology of the systemic inflammatory response syndrome (SIRS) which is caused by disseminated vascular endothelial damage. Clinical studies have shown that urinary nitrite (NO2-) and nitrate (NO3-) excretions can be utilized as indexes of NO formation. The SIRS and NO relationship was investigated in 15 neonates with SIRS, gestational age 32.5 +/- 4.4 weeks and weight 1,737 +/- 753 g. The control group comprised 18 neonates with a gestational age of 32.8 +/- 3.5 weeks and a weight of 1,778 +/- 538 g. There was no significant difference in birth weights and gestational ages between the two groups (p > 0.05 and p > 0.05). The urinary nitrite levels obtained in the subjects were normalized for urinary creatinine concentrations. The mean urinary nitrite levels in the control group neonates were found to be 4.22 +/- 1.8 micromol/mmol creatinine on the 1st day, 4.09 +/- 2.28 on the 2nd, 3.62 +/- 1.6 on the 3rd, and 4.01 +/- 1.12 micromol/mmol creatinine on the 7th day. There were no statistically significant differences between these levels (p > 0.05). We determined urinary levels of nitrite in neonates in the study group within the first 24 h of SIRS symptoms and found these levels (18.35 +/- 11.16 micromol nitrite/mmol creatinine) to be elevated as compared with those of the control subjects on the 7th day of life (p < 0.0005). In conclusion, urinary nitrite excretion is significantly elevated in neonates with SIRS due to septic events, and these results suggest that NO might play a part in SIRS.

Birth Weight↗

PubMed2005

NO generation from nitrite and its role in vascular control.

NO generated from L-arginine by NO synthases (NOSs) in the endothelium and in other cells plays a central role in several aspects of vascular biology. The biological activity of NO is acutely terminated by oxidation to nitrite and nitrate, and these compounds have long been considered only as inert end-products of NO. However, this dogma is now being challenged because recent research convincingly has shown that the nitrite ion can be recycled back to bioactive NO again in blood and tissues. Nitrite reduction to NO can occur via several routes involving enzymes, proteins, vitamins, or even simple protons. This pathway may serve as a backup system for NO generation in conditions such as hypoxia, in which the NOS/L-arginine system is compromised, but detrimental effects can also be foreseen. With this new knowledge, nitrate and nitrite should probably be viewed as storage pools for NO rather than inert waste products. Here we discuss novel aspects of nitrite-dependent NO generation in vivo and its role in vascular control.

Animals↗

PubMed2006

Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology and therapeutics.

The ability of oxyhemoglobin to inhibit nitric oxide (NO)-dependent activation of soluble guanylate cyclase and vasodilation provided some of the earliest experimental evidence that NO was the endothelium-derived relaxing factor (EDRF). The chemical behavior of this dioxygenation reaction, producing nearly diffusion limited and irreversible NO scavenging, presents a major paradox in vascular biology: The proximity of large amounts of oxyhemoglobin (10 mmol/L) to the endothelium should severely limit paracrine NO diffusion from endothelium to smooth muscle. However, several physical factors are now known to mitigate NO scavenging by red blood cell encapsulated hemoglobin. These include diffusional boundaries around the erythrocyte and a red blood cell free zone along the endothelium in laminar flowing blood, which reduce reaction rates between NO and red cell hemoglobin by 100- to 600-fold. Beyond these mechanisms that reduce NO scavenging by hemoglobin within the red cell, 2 additional mechanisms have been proposed suggesting that NO can be stored in the red blood cell either as nitrite or as an S-nitrosothiol (S-nitroso-hemoglobin). The latter controversial hypothesis contends that NO is stabilized, transported, and delivered by intra-molecular NO group transfers between the heme iron and beta-93 cysteine to form S-nitroso-hemoglobin (SNO-Hb), followed by hypoxia-dependent delivery of the S-nitrosothiol in a process that links regional oxygen deficits with S-nitrosothiol-mediated vasodilation. Although this model has generated a field of research examining the potential endocrine properties of intravascular NO molecules, including S-nitrosothiols, nitrite, and nitrated lipids, a number of mechanistic elements of the theory have been challenged. Recent data from several groups suggest that the nitrite anion (NO2-) may represent the major intravascular NO storage molecule whose transduction to NO is made possible through an allosterically controlled nitrite reductase reaction with the heme moiety of hemoglobin. As subsequently understood, the hypoxic generation of NO from nitrite is likely to prove important in many aspects of physiology, pathophysiology, and therapeutics.

Anemia, Hemolytic↗

PubMed2004

Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of the nitrite anion.

While it has long been known that the reduction of nitrite to nitric oxide (NO) forms iron-nitrosyl-myoglobin and is the basis of meat curing, a greater biological activity of the nitrite anion has only recently been appreciated. In the stomach, NO is formed from acidic reduction of nitrite and increases mucous barrier thickness and gastric blood flow (see the related study beginning on page 106). Nitrite levels in blood reflect NO production from endothelial NO synthase enzymes, and recent data suggest that nitrite contributes to blood flow regulation by reaction with deoxygenated hemoglobin and tissue heme proteins to form NO.

Animals↗

PubMed1995

Effect of wilting and processing on the nitrate and nitrite contents of some Nigerian leaf vegetables.

Nitrate and nitrite contents of seven varieties of commonly consumed leaf vegetables were determined. Effect of cooking and wilting on the contents of these factors were investigated. Nitrate ranged from 48.10 in ewuro to 270.0 ppm ogunmo (mean 116.43+/- 78.31) while nitrite ranged from 0.024 ppm in tete to 0.064 in ogunmo (mean 0.044+/-0.018). Cooking reduced the nitrate levels in all the samples but nitrite levels inexplicably increased in all sample. On wilting nitrate levels decrease while nitrite levels increased up to 83% in tete. The nitrate and nitrite levels were not considered hazardous but toxicological implications of high consumption of these factors is briefly highlighted.

Animals↗

PubMed1980

A study on the etiological factors of bilharzial bladder cancer in Egypt: 5-urinary nitrite in a rural population.

Urinary nitrite was present in 5.6% of 2379 individuals from a rural population infested with "Schistosoma haematobium". A higher frequency was observed in symptomatic patients with active bilharzial cystitis (25%) and patients with bladder cancer associated with schistosomiasis (66.2%); conversely, urinary nitrite was absent in normal urban individuals. The frequency of urinary nitrite was higher in females (6.4%) than males (4.6%), and was more frequent in adults than extremes of age. The presence of urinary nitrite was associated with urinary infection and was commonly accompanied by cellular atypia in urine, in the form of dysplasia. Under these circumstances, carcinogenic nitrosamines are liable to be produced in the bladder from urinary nitrite and amines. These observation support the possible role of urinary bacterial infection, commonly associated with bilharzial cystitis, in bladder carcinogenesis.

Adolescent↗

PubMed2003

Destruction of parotid glands affects nitrate and nitrite metabolism.

The role of salivary glands in nitrate and nitrite metabolism is poorly understood. The aim of the present study was to investigate the effect of parotid gland ablation on dynamic metabolism of nitrate and nitrite in miniature pigs. The parotid glands of 5 healthy miniature pigs were bilaterally ablated by methyl violet. Concentrations of nitrate and nitrite of whole saliva, serum, and urine samples were analyzed by high-performance liquid chromatography. Results showed that bilateral ablation of the parotid glands led to a significant decrease of nitrate secretion from blood to saliva (P < 0.05) and thus low nitrite levels. Dysfunction of the parotid glands temporarily increased the systemic level of nitrate in miniature pigs after nitrate loading. This study suggests that the parotid glands play an important role in the balance of nitrate and nitrite levels in both whole saliva and the body.

Animals↗

PubMed2002

Elevated nitrite in breath condensates of children with respiratory disease.

The aim of the study was to determine the differences in nitrite, in the exhaled breath condensates of healthy children and those children with asthma, cystic fibrosis (CF) and nonasthmatic, episodic cough. Breath condensates were obtained from 66 children (43 males:23 females, 3.1-16 yrs) and included 29 asthmatics, 12 clinically stable CF patients, 12 children with cough but not asthma and 13 healthy volunteers. The collected condensate was assayed colourimetrically using the Griess reaction to determine nitrite concentrations. Patients with CF (median: 5-95% percentiles; 2.02: 0.43-6.37 microM) or asthma (2.10: 0.63-5.45 microM) had significantly higher levels of nitrite compared to healthy subjects (0.41: 0.13-1.83 microM; p<0.05) or subjects with cough (0.75: 0.03-1.75 microM; p<0.05). Airway inflammation, as assessed by the nitrite in breath condensates, is present in children with asthma and cystic fibrosis, but not those children with nonasthmatic, episodic cough. Nitrite can be conveniently, cheaply and rapidly measured in breath condensates of children as young as 3 yrs of age, and may prove useful for the assessment of airway inflammation in children with respiratory disease.

Adolescent↗

PubMed2005

Perfusion of the isolated trout heart coronary circulation with red blood cells: effects of oxygen supply and nitrite on coronary flow and myocardial oxygen consumption.

A method for perfusion of the isolated trout heart coronary circulation with red blood cells (RBCs) was developed. The method was used to analyse the influence of RBC perfusion on myocardial O(2) supply and O(2) consumption and to test the hypothesis that nitrite is converted to vasoactive nitric oxide in the RBC-perfused coronary circulation. Perfusion with RBCs significantly increased myocardial O(2) supply and O(2) consumption by increasing the incoming O(2) concentration and the O(2) extraction. Coronary flow did not differ between RBC perfusion and saline perfusion, but RBC perfusion established a strong linear increase in myocardial O(2) consumption with coronary flow. Nitric oxide was measured in the atrial effluent of the preparation. Perfusion with saline under hypoxic conditions was associated with NO production. The nitric oxide synthase inhibitor L-NA obliterated this NO production and significantly decreased coronary flow, showing that the NO was vasoactive and probably of endothelial origin. RBC perfusion at low P(O(2)) similarly caused an L-NA-inhibitable NO production. The change in NO production upon subsequent nitrite addition, by contrast, was not inhibited by L-NA. Nitrite entered trout erythrocytes independent of degree of oxygenation, but the O(2) saturation of RBCs showed a major decrease in the coronary circulation, and [NO(2)(-)] decreased while methaemoglobin rose, suggesting that deoxyHb-mediated reduction of nitrite to NO may have occurred. However, other possibilities (e.g. NO(2)(-)-->NO conversion in myocardial cells) cannot be excluded. The NO formation associated with nitrite had no effect on coronary flow, possibly because NO was produced after the resistance vessels.

Analysis of Variance↗

PubMed1994

Nitrite inhalants: history, epidemiology, and possible links to AIDS.

Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Oxidative modification of low-density lipoprotein: lipid peroxidation by myeloperoxidase in the presence of nitrite.

Oxidative modification of low-density lipoprotein (LDL) is a pivotal process in early atherogenesis and can be brought about by myeloperoxidase (MPO), which is capable of reacting with nitrite, a NO metabolite. We studied MPO-mediated formation of conjugated dienes in isolated human LDL in dependence on the concentrations of nitrite and chloride. This reaction was strongly stimulated by low concentrations (5-50 microM) of nitrite which corresponds to the reported concentration in the arterial vessel wall. Under these conditions no protein tyrosine nitration occurred; this reaction required much higher nitrite concentrations (100 microM-1 mM). Chloride neither supported lipid peroxidation alone nor was its presence mandatory for the effect of nitrite. We propose a prominent role of lipid peroxidation for the proatherogenic action of the MPO/nitrite system, whereas peroxynitrite may be competent for protein tyrosine nitration of LDL. Monomeric and oligomeric flavan-3-ols present in cocoa products effectively counteracted, at micromolar concentrations, the MPO/nitrite-mediated lipid peroxidation of LDL. Flavan-3-ols also suppressed protein tyrosine nitration induced by MPO/nitrite or peroxynitrite as well as Cu2+-mediated lipid peroxidation of LDL. This multi-site protection by (-)-epicatechin or other flavan-3-ols against proatherogenic modification of LDL may contribute to the purported beneficial effects of dietary flavan-3-ols for the cardiovascular system.

Dose-Response Relationship, Drug↗

PubMed2006

Nitrite, a naturally occurring precursor of nitric oxide that acts like a 'prodrug'.

There are enzymatic and non-enzymatic mechanisms that generate NO* from nitrite in blood, stomach, saliva, urine and skin. In blood vessels, nitrite-derived NO* can provide protection via compensatory vasodilation during hypoxia, and in various body fluids it may have antibacterial activity. In the skin, nitrite-derived NO* may contribute to skin tanning, as well as to protection against UV-induced cell damage. Current knowledge on nitrite acting like an NO* 'prodrug' is presented, emphasizing the role of nitrite in skin.

Animals↗