Normoxic stabilization of hypoxia-inducible factor-1 expression and activity: redox-dependent effect of nitrogen oxides.

Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor involved in the oxygen-dependent regulation of gene expression. Thiol groups in HIF-1 or in proteins that modify HIF-1 are conventional targets for regulation by nitric oxide (NO). Moreover, NO delivery to tissue by hemoglobin appears to be oxygen dependent.

Elevated nitric oxide metabolite levels in chronic sinusitis.

Decreased exhaled nitric oxide (NO) is found in chronic sinusitis. NO metabolites (nitrates, nitrites, and S-nitrosothiols) were measured in sinus lavages with a rabbit model of chronic sinusitis. NO metabolite levels (mean +/- SD) were 3.

S-nitrosoglutathione breakdown prevents airway smooth muscle relaxation in the guinea pig.

Airway levels of the endogenous bronchodilator S-nitrosoglutathione (GSNO) are low in children with near-fatal asthma. We hypothesized that GSNO could be broken down in the lung and that this catabolism could inhibit airway smooth muscle relaxation. In our experiments, GSNO was broken down by guinea pig lung homogenates, particularly after ovalbumin sensitization (OS).

Airway nitrogen oxide measurements in asthma and other pediatric respiratory diseases.

Markers for airway inflammation that can be measured noninvasively in expired air may be helpful in treating patients with asthma. For example, levels of nitric oxide are high in the breath of children with asthma exacerbations and decrease with anti-inflammatory therapy. Expired nitric oxide testing has now been standardized and may be useful for children with recurring wheezing that is diagnostically or therapeutically challenging.

Endogenous nitric oxide in allergic airway disease.

There has been intense research into the role nitric oxide (NO) plays in physiologic and pathologic mechanisms. The presence of NO in exhaled breath and the high concentrations in nasal airways stimulated many studies examining exhaled and nasal NO as potential markers of airway inflammation, enabling repeated monitoring of airway inflammation not possible with invasive tests (eg, bronchoscopy). In airway inflammation, NO is not merely a marker but may have anti-inflammatory and proinflammatory effects.

Endogenous airway acidification. Implications for asthma pathophysiology.

Airway concentrations of many reactive nitrogen and oxygen species are high in asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivities/cytotoxicities of endogenous nitrogen oxides.

Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function.

Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.

Nitric oxide and thiol groups.

S-Nitroso(sy)lation reactions have recently been appreciated to regulate protein function and mediate 'nitrosative' stress. S-Nitrosothiols (SNOs) have been identified in a variety of tissues, and represent a novel class of signaling molecules which may act independently of homolytic cleavage to NO - and, indeed, in a stereoselective fashion - or be metabolized to other bioactive nitrogen oxides. It is now appreciated that sulfur-NO interactions have critical physiological relevance to mammalian neurotransmission, ion channel function, intracellular signaling and antimicrobial defense.

Umbilical arterial S-nitrosothiols in stressed newborns: role in perinatal circulatory transition.

S-Nitrosothiols are potent endogenous vasodilators recently found to be in greater concentrations in fetal umbilical venous than arterial blood. We hypothesized that neonatal increases in SNOs may be involved in the normal human perinatal circulatory transition. Paired human umbilical artery and vein plasma samples were collected after birth.

Vital capacity reservoir and online measurement of childhood nitrosopnea are linearly related. Clinical implications.

Hypernitrosopnea, a robust marker for childhood asthma, is measured reproducibly in mixed vital capacity (VC) expirates. Recent guidelines for measurement of expired nitric oxide (NO) in adults have favored use of an online (OL), flow-dependent technique. We compared VC and OL NO measurements in 14 asthmatic and 11 control children 5 through 18 yr of age.

Reductive assays for S-nitrosothiols: implications for measurements in biological systems.

Bioactive SNOs are found in many tissues. We speculated SNOs might be misidentified in conventional assays which reduce NO-3 to NO. S-Nitrosothiols were exposed to saturated VCl3 in HCl, 1% KI in acetic acid, photolysis, or CuCl and CSH in He; NO was measured by chemiluminescence.

Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure.

Background: Nitric oxide (NO) gas concentrations are high in the expired air of individuals with asthma, but not consistently so in the expired air of people with pneumonia. S-nitrosothiols are naturally occurring bronchodilators, the concentrations of which are raised in the airways of patients with pneumonia. Airway S-nitrosothiols have not been studied in asthma.

Braided bronchus: a previously undescribed airway anomaly.

Infants with congenital heart disease frequently experience recurrent atelectasis, in many cases associated with anomalous branching of the bronchial tree. The bridging bronchus has been well described and has been associated with both left-sided obstructive lesions and a sling-like left pulmonary artery. We describe a similar, though distinct airway anomaly, the "braided bronchus," associated with a bridging bronchus in a child with coarctation of the aorta and recurrent atelectasis.

Expired nitric oxide as a marker for childhood asthma.

Expression of the inflammatory isoform of the enzyme nitric oxide synthase (NOS) is increased in airway-lining cells of patients with asthma. The NOS product nitric oxide (NO.) was measured in the expired gas of children with asthma.

Polynitrosylated proteins: characterization, bioactivity, and functional consequences.

Chemical modification of proteins is a common theme in their regulation. Nitrosylation of protein sulfhydryl groups has been shown to confer nitric oxide (NO)-like biological activities and to regulate protein functions. Several other nucleophilic side chains -- including those with hydroxyls, amines, and aromatic carbons -- are also potentially susceptible to nitrosative attack.

Expired nitric oxide levels during treatment of acute asthma.

Nitric oxide (NO) is known to be present in measurable quantities in the exhaled air of normal subjects and at higher concentrations in asthmatic subjects not treated with glucocorticoids. We confirmed these findings by analyzing the mean mixed expired NO concentrations of 43 stable asthmatics and 90 normal subjects; NO levels were higher in the asthmatic population (13.9 parts per billion [ppb] versus 6.

Chemical regulation of pulmonary airway tone.

Over the past three years, substantial progress has been made in dissecting out the role of each of these individual effector systems, namely, the leukotrienes, neuropeptides, and nitrogen oxides. The next major challenge is to understand how they function in an integrated fashion.

Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells.

Histochemical activity and immunoreactivity of nitric oxide synthase (NOS, EC 1.14.13.

Relaxation of human bronchial smooth muscle by S-nitrosothiols in vitro.

S-Nitrosothiols (RS-NO) relax tracheal smooth muscle from a variety of animal species, and may have physiological relevance. We therefore studied their effects on human bronchial smooth muscle. S-Nitroso adducts of glutathione, cysteine, N-acetylcysteine and bovine serum albumin relaxed tissues contracted with methacholine with mean IC50 +/- S.

The biology of nitrogen oxides in the airways.

Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung. The relationship between the toxicities and the bioactivities of NOx must be understood in the context of their chemical interactions in the pulmonary microenvironment. Nitric oxide synthase (NOS) is a newly identified enzyme system active in airway epithelial cells, macrophages, neutrophils, mast cells, autonomic neurons, smooth muscle cells, fibroblasts, and endothelial cells.