Assessment of exhaled nitric oxide kinetics in healthy infants.

Exhaled nitric oxide (Fe(NO)) measurements provide a noninvasive approach to the evaluation of airway inflammation. Flow-independent NO exchange parameters [airway NO transfer factor (D(NO)) and airway wall NO concentration (Cw(NO))] can be estimated from Fe(NO) measurements at low flows and may elucidate mechanisms of disturbances in NO exchange. We measured Fe(NO) in sedated infants by using an adaptation of a raised lung volume rapid thoracic compression technique that creates forced expiration through a mass-flow controller that lasts 5-10 s, at a constant preset flow. We measured Fe(NO) at expired flows of 50, 25, and 15 ml/s in five healthy infants (7-31 mo). Median Fe(NO) increased [24, 40, and 60 parts per billion (ppb)] with decreasing expiratory flows (50, 25, and 15 ml/s). Group median (range) for D(NO) and Cw(NO) were 12.7 (3.2-37) x 10(-3) nl. s(-1). ppb(-1) and 108.9 (49-385) ppb, respectively, similar to values reported in healthy adults. Exhaled NO is flow dependent; flow-independent parameters of exhaled NO kinetics can be assessed in infants and are similar to values described in adults.     

Temperature conditioning of nasal air: effects of vasoactive agents and involvement of nitric oxide.

Nitric oxide (NO) is released into nasal air, but its function is unknown. We hypothesized that nasal vascular tone and/or flow influences temperature conditioning of nasal air and that NO participates in this process. We measured nasal air temperature (via a thermocouple) and exhaled nasal NO release (by chemiluminescence) in five humans and examined the effects of an aerosolized vasoconstrictor (oxymetazoline), a vasodilator (papaverine), N(G)-nitro-L-arginine methyl ester, an inhibitor of NO synthase, or saline (control). Compared with saline (which caused no changes in nasal air temperature or exhaled NO release), oxymetazoline (0.05%) reduced nasal air temperature and NO release (130.8 +/- 15.1 to 81.3 +/- 12.8 nl. min(-1). m(-2); P < 0.01). Papaverine (0.01 M) increased nasal air temperature and NO release (131.8 +/- 13.1 to 157.2 +/- 17.4 nl. min(-1). m(-2); P < 0.03). N(G)-nitro-L-arginine methyl ester reduced nasal air temperature and NO release (123.7 +/- 14.2 to 44.2 +/- 23.7 nl. min(-1). m(-2); P < 0.01). The results suggest that vascular tone and/or flow modulates temperature conditioning and that NO may participate in that function.     

Flow-independent nitric oxide exchange parameters in healthy adults.

Currently accepted techniques utilize the plateau concentration of nitric oxide (NO) at a constant exhalation flow rate to characterize NO exchange, which cannot sufficiently distinguish airway and alveolar sources. Using nonlinear least squares regression and a two-compartment model, we recently described a new technique (Tsoukias et al. J Appl Physiol 91: 477-487, 2001), which utilizes a preexpiratory breath hold followed by a decreasing flow rate maneuver, to estimate three flow-independent NO parameters: maximum flux of NO from the airways (J(NO,max), pl/s), diffusing capacity of NO in the airways (D(NO,air), pl x s(-1) x ppb(-1)), and steady-state alveolar concentration (C(alv,ss), ppb). In healthy adults (n = 10), the optimal breath-hold time was 20 s, and the mean (95% intramaneuver, intrasubject, and intrapopulation confidence interval) J(NO,max), D(NO,air), and C(alv,ss) are 640 (26, 20, and 15%) pl/s, 4.2 (168, 87, and 37%) pl x s(-1) x ppb(-1), and 2.5 (81, 59, and 21%) ppb, respectively. J(NO,max) can be estimated with the greatest certainty, and the variability of all the parameters within the population of healthy adults is significant. There is no correlation between the flow-independent NO parameters and forced vital capacity or the ratio of forced expiratory volume in 1 s to forced vital capacity. With the use of these parameters, the two-compartment model can accurately predict experimentally measured plateau NO concentrations at a constant flow rate. We conclude that this new technique is simple to perform and can simultaneously characterize airway and alveolar NO exchange in healthy adults with the use of a single breathing maneuver.     

Production and absorption of nitric oxide gas in the nose

Some nitric oxide gas (NO) produced in thesinuses and nasal cavity is absorbed before leaving the nose. Tomeasure production and absorption, we introduced NO at differentconcentrations into one nostril while sampling the NO leaving theopposite nostril with the soft palate closed. The quantity of NO gasproduced in six normal subjects (amount leaving plus the amountabsorbed) averaged 352 nl/min and was the same at gas flows rangingfrom 8 to 347 ml/min and at 10 l/min. An absorption coefficientA was calculated by dividing theamount of NO absorbed by the concentration leaving the nose.A ranged from 17 ml/min at a nasal gasflow of 8 ml/min to an A of 24 ml/minat a nasal gas flow of 347 ml/min. The calculated rates of productionand absorption did not change when gas flow rate was increased,suggesting diffusion equilibrium. The amount of uptake of NO in thenasal mucosa can be explained by its solubility coupled with tissue andblood reactivity.

     

Low nitric oxide concentrations in exhaled gas and nasal airways of mammals without paranasal sinuses

To investigatewhether relevant levels of nasal nitric oxide (NO) are produced in theabsence of paranasal sinuses, we studied 17 healthy baboons, mammalswithout any paranasal sinuses. The animals were anesthetized withketamine hydrochloride and breathed spontaneously. While the baboonsbreathed through a face mask (mouths closed) connected to a respirator,NO concentrations in exhaled gas were sampled from the expiratory limband analyzed by chemiluminescence. While the animals were breathingambient air, nasal gas was sampled via a thin plastic tube and analyzed for NO concentrations by chemiluminescence. Mean NO concentration inthe exhaled gas was 1.00 ± 0.59 parts/billion, and NO release was4.28 ± 2.72 nl/min. A NO concentration of 4.79 ± 2.08 parts/billion was found in the nasal gas (NO release: 7.18 ± 3.13 nl/min). An age-dependent increase in nasal NO levelswas not observed. Exhaled and nasal NO concentrations in baboons weremarkedly lower than in mammals with paranasal sinuses, suggesting thatparanasal sinuses might be an anatomic requirement for production ofrelevant nasal NO levels.

     

Mucus secretion from single submucosal glands of pig. Stimulation by carbachol and vasoactive intestinal peptide

Secretion rates of >700 individual glands in isolated tracheal mucosa from 56 adult pigs were monitored optically. "Basal" secretion of 0.7 +/- 0.1 nl x min(-1) gland(-1) was observed 1-9 h post-harvest but was near zero on day 2. Secretion to carbachol (10 microm) peaked at 2-3 min and then declined to a sustained phase. Peak secretion was 12.4 +/- 1.1 nl x min(-1) gland(-1); sustained secretion was approximately one-third of peak secretion. Thapsigargin (1 microm) increased secretion from 0.1 +/- 0.05 to 0.7 +/- 0.2 nl x min(-1) gland(-1); thapsigargin did not cause contraction of the trachealis muscles. Isoproterenol and phenylephrine (10 microm each) were ineffective, but vasoactive intestinal peptide (1 microm) and forskolin (10 microm) each produced sustained secretion of 1.0 +/- 0.5 and 1.7 +/- 0.2 nl x min(-1) gland(-1), respectively. The density of actively secreting glands was 1.3/mm(2). Secretion to either carbachol or forskolin was inhibited (approximately 50%) by either bumetanide or HCO(3)(-) removal and inhibited approximately 90% by the combined treatments. Mucus secreted in response to carbachol or forskolin was acidic by approximately 0.2 pH units relative to the bath and remained acidic by approximately 0.1 pH units after bumetanide. The strong secretory response to vasoactive intestinal peptide, the acidity of [cAMP](i)-stimulated mucus, and its inhibition by bumetanide were unexpected.     

Nasal nitric oxide levels in cystic fibrosis patients are associated with a neuronal NO synthase (NOS1) gene polymorphism.

Nitric oxide (NO) plays an important role in a number of physiological processes in the airways, including host defense. Although the exact cellular and molecular source of the NO formation in airways is unknown, there is recent evidence that neuronal NO synthase (NOS1) contributes significantly to NO in the lower airways of cystic fibrosis (CF) patients. NOS1 protein has been shown to be expressed in nasal epithelium, suggesting an involvement of NOS1-derived NO in upper airway biology. We here hypothesized that nasal NO concentrations in CF patients are related to genotype variants in the NOS1 gene. Measurements of nasal NO concentration and pulmonary function were performed in 40 clinically stable CF patients. Genomic DNA from all patients was screened for an intronic AAT-repeat polymorphism in the NOS1 gene using polymerase chain reaction and simple sequence length polymorphism (SSLP) analysis. The allele size at that locus was significantly (P = 0.001) associated with upper airway NO. Mean (+/- SD) nasal NO concentrations were 40.5 +/- 5.2 ppb in CF patients (n = 12) with high repeat numbers (i.e., both alleles > or =12 repeats) and 72.6 +/- 7.4 ppb in patients (n = 28) with low repeat numbers (i.e., at least one allele <12 repeats). Furthermore, in the group of CF patients harboring NOS1 genotypes associated with low nasal NO, colonization of airways with P. aeruginosa was significantly more frequent than in patients with NOS1 genotypes associated high nasal NO concentrations (P = 0.0022). We conclude that (1) the variability in CF nasal NO levels are related to naturally occurring variants in the NOS1 gene, and (2) that nasal NOS1-derived NO affects the susceptibility of CF airways to infection with P. aeruginosa.     

Differential role of nitric oxide in regional sympathetic responses to stimulation of NTS A2a adenosine receptors

Our previous studies showed that preganglionic adrenal (pre-ASNA), renal (RSNA), lumbar, and postganglionic adrenal sympathetic nerve activities (post-ASNA) are inhibited after stimulation of arterial baroreceptors, nucleus of the solitary tract (NTS), and glutamatergic and P2x receptors and are activated after stimulation of adenosine A1 receptors. However, stimulation of adenosine A2a receptors inhibited RSNA and post-ASNA, whereas it activated pre-ASNA. Because the effects evoked by NTS A2a receptors may be mediated via activation of nitric oxide (NO) mechanisms in NTS neurons, we tested the hypothesis that NO synthase (NOS) inhibitors would attenuate regional sympathetic responses to NTS A2a receptor stimulation, whereas NO donors would evoke contrasting responses from pre-ASNA versus RSNA and post-ASNA. Therefore, in chloralose/urethane-anesthetized rats, we compared hemodynamic and regional sympathetic responses to microinjections of selective A2a receptor agonist (CGS-21680, 20 pmol/50 nl) after pretreatment with NOS inhibitors Nomega-nitro-L-arginine methyl ester (10 nmol/100 nl) and 1-[2-(trifluoromethyl)phenyl]imidazole (100 pmol/100 nl) versus pretreatment with vehicle (100 nl). In addition, responses to microinjections into the NTS of different NO donors [40 and 400 pmol/50 nl sodium nitroprusside (SNP); 0.5 and 5 nmol/50 nl 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (DETA NONOate, also known as NOC-18), and 2 nmol/50 nl 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (PAPA NONOate, also known as NOC-15)], the NO precursor L-arginine (10-50 nmol/50 nl), and sodium glutamate (500 pmol/50 nl) were evaluated. SNP, DETA NONOate, and PAPA NONOate activated pre-ASNA and inhibited RSNA and post-ASNA, whereas l-arginine and glutamate microinjected into the same site of the NTS inhibited all these sympathetic outputs. Decreases in heart rate and depressor or biphasic responses accompanied the neural responses. Pretreatment with NOS inhibitors reversed the normal depressor and sympathoinhibitory responses to stimulation of NTS A2a receptors into pressor and sympathoactivatory responses and attenuated the heart rate decreases; however, it did not change the increases in pre-ASNA. We conclude that NTS NO mechanisms differentially affect regional sympathetic outputs and differentially contribute to the pattern of regional sympathetic responses evoked by stimulation of NTS A2a receptors.     

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox.

Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21-38 yr old, n = 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (Ca(NO)) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50-500 ml/s), the slope has been previously interpreted as a nonzero Ca(NO) (range 1-5 ppb); however, the trumpet model predicts a positive slope of 0.4-2.1 ppb despite a zero Ca(NO) because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO.     

N omega-nitro-L-arginine influences cerebral metabolism in awake sheep.

Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor-nitric oxide (NO). An inhibitor of NO formation, N omega-nitro-L-arginine (LNA, 100 micrograms/kg i.v.), was given to conscious sheep (n = 6) during normoxia and again in hypocapnic hypoxia (arterial PO2 approximately 38 Torr). Blood samples were obtained from the aorta and sagittal sinus, and cerebral blood flow (CBF) was measured with 15-microns radiolabeled microspheres. During normoxia, LNA elevated (P < 0.05) mean arterial pressure from 82 +/- 3 to 88 +/- 2 (SE) mmHg and cerebral perfusion pressure (CPP) from 72 +/- 3 to 79 +/- 3 mmHg, CBF was unchanged, and cerebral lactate release (CLR) rose temporarily from 0.0 +/- 1.9 to 13.3 +/- 8.7 mumol.min-1 x 100 g-1 (P < 0.05). The glucose-O2 index declined (P < 0.05) from 1.67 +/- 0.16 to 1.03 +/- 0.4 mumol.min-1 x 100 g-1. Hypoxia increased CBF from 59.9 +/- 5.4 to 122.5 +/- 17.5 ml.min-1 x 100 g-1 and the glucose-O2 index from 1.75 +/- 0.43 to 2.49 +/- 0.52 mumol.min-1 x 100 g-1 and decreased brain CO2 output, brain respiratory quotient, and CPP (all P < 0.05), while cerebral O2 uptake, CLR, and CPP were unchanged. LNA given during hypoxia decreased CBF to 77.7 +/- 11.8 ml.min-1 x 100 g-1 and cerebral O2 uptake from 154 +/- 22 to 105.2 +/- 12.4 mumol.min-1 x 100 g-1 and further elevated mean arterial pressure to 98 +/- 2 mmHg (all P < 0.05), CLR was unchanged, and, surprisingly, brain CO2 output and respiratory quotient were reduced dramatically to negative values (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

A microbiological study of an underground gas storage in the process of gas injection

The liquid phase of different units of an underground gas storage (UGS) in the period of gas injection was studied with respect to its hydrochemical composition and characterized microbiologically. The presence of viable aerobic and anaerobic bacteria was revealed in the UGS stratal and associated waters. An important source of microorganisms and biogenic elements in the ecosystem studied is water and various technogenic admixtures contained in trace amounts in the gas entering from the gas main in the period of gas injection into the storage. Owing to this fact, the bacterial functional diversity, number, and activity are maximal in the system of gas treatment and purification and considerably lower in the observation well zone. At the terminal stages, the anaerobic transformation of organic matter in the UGS aqueous media occurs via sulfate reduction and methanogenesis; exceptionally high rates of these processes (up to 4.9 x 10(5) ng S(2-)l(-1) day(-1) and 2.8 x 10(6) nl CH4 l(-1) day(-1), respectively) were recorded for above-ground technological equipment.     

Determination of production of nitric oxide by lower airways of humans---theory

Hyde, Richard W., Edgar J. Geigel, Albert J. Olszowka, JohnA. Krasney, Robert E. Forster II, Mark J. Utell, and Mark W. Frampton.Determination of production of nitric oxide by the lower airwaysof humanstheory. J. Appl. Physiol.82(4): 1290-1296, 1997.Exercise and inflammatory lung disorderssuch as asthma and acute lung injury increase exhaled nitric oxide(NO). This finding is interpreted as a rise in production of NO by thelungs (NO)but fails to take into account the diffusing capacity for NO(DNO) that carries NO into thepulmonary capillary blood. We have derived equations to measureNO from thefollowing rates, which determine NO tension in the lungs(PL) at any moment from 1) production(NO);2) diffusion, whereDNO(PL) = rate of removal by lung capillary blood; and3) ventilation, whereA(PL)/(PB  47) = the rate of NO removal by alveolar ventilation(A) and PB is barometric pressure. During open-circuit breathingwhen PL is not in equilibrium,d/dtPL[V_L/(PB  47)] (where V_L is volumeof NO in the lower airways) = NO  DNO(PL)  A(PL)/(PB  47). When PL reaches asteady state so that d/dt = 0 andA iseliminated by rebreathing or breath holding, then PL = NO/DNO.PL can be interpreted as NOproduction per unit of DNO. Thisequation predicts that diseases that diminishDNO but do not alterNO willincrease expired NO levels. These equations permit precise measurementsof NO thatcan be applied to determining factors controlling NO production by thelungs.

     

NO supports right ventricular flow dominance and whole body O(2) utilization in midgestation fetal lambs

It is unknown if nitric oxide (NO) modulates the relative levels of left (LV) and right (RV) ventricular output, fetal O2 consumption, or blood flow distribution between the body and placenta at midgestation. To address these questions, six fetal lambs were instrumented at 89-96 days gestation (term 147 days), and blood flows were measured with radioactive microspheres 3-4 days later at baseline and after inhibition of NO synthesis with 10 mg/kg (L-NNA10) and 25 mg/kg (L-NNA25) N(omega)-nitro-L-arginine. LV output fell by 74 +/- 15 ml. min(-1). kg(-1) at L-NNA10 (P < 0.005), whereas RV output decreased by 90 +/- 18 ml. min(-1). kg(-1) at L-NNA10 (P < 0.02) and by a further 80 +/- 22 ml. min(-1). kg(-1) at L-NNA25 (P < 0.05). As a result, RV output exceeded LV output at baseline (P = 0.03) and L-NNA10 (P < 0.02) but not at L-NNA25. Fetal body blood flow fell by 95 +/- 25 ml. min(-1). kg(-1) at L-NNA10 (P < 0.01), but because placental blood flow decreased by 70 +/- 22 ml. min(-1). kg(-1) at L-NNA10 (P < 0.01) and a further 71 +/- 21 ml. min(-1). kg(-1) at L-NNA25 (P < 0.01), the fetal body-to-placental blood flow ratio was near unity at baseline and L-NNA10 but rose to 1.5 +/- 0.3 at L-NNA25 (P < 0.05). In association with these flow changes, fetal O2 consumption declined by 1.4 +/- 0.3 ml. min(-1). kg(-1) at L-NNA10 (P < 0.05) and by a further 1.5 +/- 0.6 ml. min(-1). kg(-1) at L-NNA25 (P < 0.02). These findings suggest that, in midgestation fetal lambs, NO supports an RV flow dominance, whole body O2 utilization, and the maintenance of a near-equal fetoplacental blood flow distribution.     

Reaction of nitric oxide with synthetic hemoprotein, human serum albumin incorporating tetraphenylporphinatoiron(II) derivatives

The reaction of nitric oxide (NO) with a synthetic hemoprotein, the recombinant human serum albumin (rHSA) incorporating eight tetraphenylporphinatoiron(II) derivatives bearing a covalently linked axial base (FeP) [rHSA-FeP], has been investigated. The UV--vis absorption spectrum of the phosphate buffer solution (pH 7.3) of rHSA-FeP showed maxima at 425 and 546 nm upon the addition of NO. The carbonyl rHSA-FeP, in which FePs are six-coordinate CO-adducts, also moved to the same species after bubbling with NO gas. ESR spectroscopy revealed that the incorporated FePs in the albumin formed six-coordinate nitrosyl complexes; the proximal imidazole moiety does not dissociate from the central iron when NO binds to the trans side. The NO-binding affinity of rHSA-FeP (P(1/2)(NO), 1.7 x 10(-6) Torr, pH 7.3, 298 K) was significantly lower than that of FeP itself (P(1/2)(NO), 1.8 x 10(-8) Torr in toluene). Kinetically, this arises from the decreased association rate constant (k(on)(NO), 8.9 x 10(8) M(-1) s(-1) --> 1.5 x 10(7) M(-1) s(-1)). Since NO-association is diffusion controlled, incorporation of the synthetic heme into the albumin matrix appears to restrict the NO access to the central iron(II).     

ATP mediates flow-induced NO production in thick ascending limbs

Mechanical stimulation caused by increasing flow induces nucleotide release from many cells. Luminal flow and extracellular ATP stimulate production of nitric oxide (NO) in thick ascending limbs. However, the factors that mediate flow-induced NO production are unknown. We hypothesized that luminal flow stimulates thick ascending limb NO production via ATP. We measured NO in isolated, perfused rat thick ascending limbs using the fluorescent dye DAF FM. The rate of increase in dye fluorescence reflects NO accumulation. Increasing luminal flow from 0 to 20 nl/min stimulated NO production from 17 ± 16 to 130 ± 37 arbitrary units (AU)/min (P < 0.02). Increasing flow from 0 to 20 nl/min raised ATP release from 4 ± 1 to 21 ± 6 AU/min (P < 0.04). Hexokinase (10 U/ml) plus glucose, which consumes ATP, completely prevented the measured increase in ATP. Luminal flow did not increase NO production in the presence of luminal and basolateral hexokinase (10 U/ml). When flow was increased with the ATPase apyrase in both luminal and basolateral solutions (5 U/ml), NO levels did not change significantly. The P2 receptor antagonist suramin (300 μmol/l) reduced flow-induced NO production by 83 ± 25% (P < 0.03) when added to both and basolateral sides. Luminal hexokinase decreased flow-induced NO production from 205.6 ± 85.6 to 36.6 ± 118.6 AU/min (P < 0.02). Basolateral hexokinase also reduced flow-induced NO production. The P2X receptor-selective antagonist NF023 (200 μmol/l) prevented flow-induced NO production when added to the basolateral side but not the luminal side. We conclude that ATP mediates flow-induced NO production in the thick ascending limb likely via activation of P2Y receptors in the luminal and P2X receptors in the basolateral membrane.     

Bioflocculation of microalgae and bacteria combined with flue gas to improve sewage treatment

Although microalgae are promising for a cradle-to-cradle design approach of sewage treatment, their application is hampered by high harvesting costs and low C:N ratios of sewage. Therefore, the potential of microalgal bacterial flocs (MaB-flocs) was investigated for the secondary treatment of sewage supplemented with different flue gas flow rates (FGFRs) from a coal power plant. Effluent (N, P, turbidity and pH) and off gas discharge levels (NO(x), SO(x)) met the European discharge limits with a hydraulic retention time of only 0.67 days and an FGFR of 0.6Lh(-1) (0.0025 vvm). This FGFR provided sufficient carbon and resulted in removal efficiencies of 48 ± 7% CO(2), 87 ± 5% NO(x) and 99 ± 1% SO(2). MaB-flocs settled fast reaching up to a density of 19 g VSSL(-1). High biomass productivities (0.18 gL(-1)day(-1)) were obtained under a low light intensity. This successful reactor performance indicates the large potential for the industrial application of MaB-flocs for flue gas sparged sewage treatment.     

NOx removal from flue gas by an integrated physicochemical absorption and biological denitrification process

An integrated physicochemical and biological technique for NO(x) removal from flue gas, the so-called BioDeNO(x) process, combines the principles of wet absorption of NO in an aqueous Fe(II)EDTA(2-) solution with biological reduction of the sorbed NO in a bioreactor. The biological reduction of NO to di-nitrogen gas (N(2)) takes place under thermophilic conditions (55 degrees C). This study demonstrates the technical feasibility of this BioDeNO(x) concept in a bench-scale installation with a continuous flue gas flow of 650 l.h(-1) (70-500 ppm NO; 0.8-3.3% O(2)). Stable NO removal with an efficiency of at least 70% was obtained in case the artificial flue gas contained 300 ppm NO and 1% O(2) when the bioreactor was inoculated with a denitrifying sludge. An increase of the O(2) concentration of only 0.3% resulted in a rapid elevation of the redox potential (ORP) in the bioreactor, accompanied by a drastic decline of the NO removal efficiency. This was not due to a limitation or inhibition of the NO reduction, but to a limited biological iron reduction capacity. The latter leads to a depletion of the NO absorption capacity of the scrubber liquor, and thus to a poor NO removal efficiency. Bio-augmentation of the reactor mixed liquor with an anaerobic granular sludge with a high Fe(III) reduction capacity successfully improved the bioreactor efficiency and enabled to treat a flue gas containing at least 3.3% O(2) and 500 ppm NO with an NO removal efficiency of over 80%. The ORP in the bioreactor was found to be a proper parameter for the control of the ethanol supply, needed as electron donor for the biological regeneration process. The NO removal efficiency as well as the Fe(III)EDTA(-) reduction rate were found to decline at ORP values higher than -140 mV (pH 7.0). For stable BioDeNO(x) operation, the supply of electron donor (ethanol) can be used to control the ORP below that critical value.     

Examining axial diffusion of nitric oxide in the lungs using heliox and breath hold.

Exhaled nitric oxide (NO) is highly dependent on exhalation flow; thus exchange dynamics of NO have been described by multicompartment models and a series of flow-independent parameters that describe airway and alveolar exchange. Because the flow-independent NO airway parameters characterize features of the airway tissue (e.g., wall concentration), they should also be independent of the physical properties of the insufflating gas. We measured the total mass of NO exhaled (A(I,II)) from the airways after five different breath-hold times (5-30 s) in healthy adults (21-38 yr, n = 9) using air and heliox as the insufflating gas, and then modeled A(I,II) as a function of breath-hold time to determine airway NO exchange parameters. Increasing breath-hold time results in an increase in A(I,II) for both air and heliox, but A(I,II) is reduced by a mean (SD) of 31% (SD 6) (P < 0.04) in the presence of heliox, independent of breath-hold time. However, mean (SD) values (air, heliox) for the airway wall diffusing capacity [3.70 (SD 4.18), 3.56 pl.s(-1).ppb(-1) (SD 3.20)], the airway wall concentration [1,439 (SD 487), 1,503 ppb (SD 644>)], and the maximum airway wall flux [4,156 (SD 2,502), 4,412 pl/s (SD 2,906)] using a single-path trumpet-shaped airway model that considers axial diffusion were independent of the insufflating gas (P > 0.55). We conclude that a single-path trumpet model that considers axial diffusion captures the essential features of airway wall NO exchange and confirm earlier reports that the airway wall concentration in healthy adults exceeds 1 ppm and thus approaches physiological concentrations capable of modulating smooth muscle tone.     

Effects of 1400W, a potent selective inducible NOS inhibitor, on histamine- and leukotriene D4-induced relaxation of isolated guinea pig nasal mucosa.

To clarify the role of inducible nitric oxide synthase (iNOS) in the relaxation of nasal vasculature, the effects of a potent selective iNOS inhibitor, N-[(3-aminomethyl)benzyl]acetamidine (1400W), on histamine- and leukotriene D4 (LTD4)-induced relaxations of isolated nasal septal mucosae were examined in naive guinea pigs. In addition to eNOS and nNOS, Western blots demonstrated a distinct expression of iNOS in nasal mucosal tissues of naive guinea pigs. In isolated nasal septal mucosae precontracted with norepinephrine (3 x 10(-5)M), both histamine (10(-7)-10(-3)M) and LTD4 (10(-10)-10(-7)M) exhibited relaxations, which were inhibited by a NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4)M). The inhibitory effect of L-NMMA was reversed by L-arginine (10(-3)M), indicating that the relaxations induced by histamine and LTD4 are mediated by NO. Furthermore, both the histamine- and LTD4-induced relaxations were also significantly attenuated by 1400W (10(-5)M). These findings suggest an involvement of NO generated by iNOS in agonist-induced relaxation of nasal mucosal vasculature in naive guinea pigs.     

Nitric oxide inhibits norepinephrine-induced hepatic vascular responses but potentiates hepatic glucose output

We previously reported that sympathetic nerve-induced vasoconstriction in the intestine resulted in shear stress induced release of nitric oxide (NO) that led to presynaptic inhibition of transmitter release. In contrast, studies in the liver suggested a postsynaptic inhibition of vascular responses, thus leading to the hypothesis tested here that maintained catecholamine release in the liver would result in maintained metabolic catecholamine action in the face of inhibition of vascular responses. In rats, norepinephrine (NE) induced elevations in arterial glucose content were inhibited by NO synthase antagonism (N(omega)-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg, intraportal) but potentiated by NO donor administration (3-morpholinosydnonimine (SIN-1), 0.2 mg/kg, intraportal). The potentiated effect of SIN-1 was abolished by indomethacin (7.5 mg/kg, intraportal). To confirm the hepatic site of metabolic effect, cats were used so that blood flow and hepatic glucose balance could be determined. SIN-1 potentiated NE-induced glucose output from the liver from 5.0 +/- 0.4 to 7.2 +/- 0.6 mg x min(-1) x kg(-1). The potentiation was blocked by methylene blue, a guanylate cyclase inhibitor. Contrary to the glucose response, L-NAME potentiated but SIN-1 attenuated NE-induced portal vasoconstriction. Thus NO is shown to produce differential modulation of vascular and metabolic effects of NE. Vasoconstriction of the hepatic vasculature is inhibited by NO, whereas the glycogenolytic response to NE is potentiated, responses that are probably mediated by prostaglandin.