Exhaled and nasal NO levels in allergic rhinitis: relation to sensitization, pollen season and bronchial hyperresponsiveness.
(41/20782)
Exhaled nitric oxide is a potential marker of lower airway inflammation. Allergic rhinitis is associated with asthma and bronchial hyperresponsiveness. To determine whether or not nasal and exhaled NO concentrations are increased in allergic rhinitis and to assess the relation between hyperresponsiveness and exhaled NO, 46 rhinitic and 12 control subjects, all nonasthmatic nonsmokers without upper respiratory tract infection, were randomly selected from a large-scale epidemiological survey in Central Norway. All were investigated with flow-volume spirometry, methacholine provocation test, allergy testing and measurement of nasal and exhaled NO concentration in the nonpollen season. Eighteen rhinitic subjects completed an identical follow-up investigation during the following pollen season. Exhaled NO was significantly elevated in allergic rhinitis in the nonpollen season, especially in perennially sensitized subjects, as compared with controls (p=0.01), and increased further in the pollen season (p=0.04), mainly due to a two-fold increase in those with seasonal sensitization. Nasal NO was not significantly different from controls in the nonpollen season and did not increase significantly in the pollen season. Exhaled NO was increased in hyperresponsive subjects, and decreased significantly after methacholine-induced bronchoconstriction, suggesting that NO production occurs in the peripheral airways. In allergic rhinitis, an increase in exhaled nitric oxide on allergen exposure, particularly in hyperresponsive subjects, may be suggestive of airway inflammation and an increased risk for developing asthma. (+info)
Nasal nitric oxide concentration in paranasal sinus inflammatory diseases.
(42/20782)
In normal upper airways, nitric oxide is generated by the paranasal sinus epithelium and then diffuses into the nasal cavities. This study examined whether or not nasal NO concentration is affected by paranasal sinus inflammatory diseases. The influence of obstruction (nasal polyposis) and/or inflammation (allergy or chronic sinusitis) of the paranasal sinuses on nasal NO concentration was evaluated in nasal allergic (n=7 patients) or nonallergic (n=20) polyposis, nonallergic chronic sinusitis (n=10) and Kartagener's syndrome (n=6) and compared with control subjects (n=42). A score of alteration of the paranasal sinus (number of altered and occluded sinuses) was determined by a computed tomography scan. The nasal NO concentration in nasal nonallergic polyposis (150+/-20 parts per billion (ppb)) was significantly decreased compared with both controls (223+/-6 ppb, p=0.01) and polyposis with allergy (272+/-28 ppb, p<0.0001). In each group, the nasal NO concentration was inversely correlated with the extent of tomodensitometric alteration of the paranasal sinuses. In Kartagener's syndrome, the nasal NO concentration (14+/-2 ppb) was drastically decreased compared with all other groups, despite the presence of open paranasal sinuses. Thus, the nasal NO concentration in patients with nasal polyposis appeared to be dependent on both the allergic status and the degree of obstruction of the paranasal sinuses. (+info)
Bradykinin-induced bronchospasm in the rat in vivo: a role for nitric oxide modulation.
(43/20782)
Bradykinin has an important role in asthma pathogenesis, but its site of action is unclear. It was previously reported by the authors that bradykinin causes a dose-dependent reduction in dynamic compliance but little change in total lung resistance. This suggested that bradykinin may have a preferential effect in the distant lung. The purpose of the current investigation was to better characterize the effects of bradykinin on pulmonary resistance in rodents and explore the role of nitric oxide release in modulating the effect of bradykinin. Airway constriction was induced in the rats by aerosol administration of bradykinin with or without treatments with the inhaled bradykinin-2 receptor antagonist, Hoe 140 or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester or N(G)-monomethyl-L-arginine. Total lung resistance was partitioned into tissue and airway resistance by using the alveolar capsule method. Bradykinin induced a significant increase in both resistances. Hoe 140 abolished the response to bradykinin. The nitric oxide synthase inhibitors enhanced the bronchoconstricting response. In conclusion, the bradykinin response in the rats was not only localized to conducting airways but also involved a relatively selective tissue reaction. Bradykinin-induced bronchospasm in the rat is solely due to activation of bradykinin-2 receptor. Further, it was shown that nitric oxide significantly modulates the bronchospasm caused by bradykinin, suggesting that nitric oxide is an important modulator of airways responsiveness to bradykinin. (+info)
Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma.
(44/20782)
Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations. Twenty-two atopic children (aged 11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2-adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per billion (ppb) and 4.0+/-0.5 ppb, respectively; p<0.01). Interestingly, 14 out of 22 asthmatic children had NO levels >8.8 ppb (i.e. >2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p<0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p>0.1, each correlation). These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established. (+info)
Salivary contribution to exhaled nitric oxide.
(45/20782)
Dietary and metabolic nitrate is distributed from the blood to the saliva by active uptake in the salivary glands, and is reduced to nitrite in the oral cavity by the action of certain bacteria. Since it has been reported that nitric oxide may be formed nonenzymatically from nitrite this study aimed to determine whether salivary nitrite could influence measurements of exhaled NO. Ten healthy subjects fasted overnight and ingested 400 mg potassium nitrate, equivalent to approximately 200 g spinach. Exhaled NO and nasal NO were regularly measured with a chemiluminescence technique up to 3 h after the ingestion. Measurements of exhaled NO were performed with a single-breath procedure, standardized to a 20-s exhalation, at a flow of 0.15 L x s(-1), and oral pressure of 8-10 cmH2O. Values of NO were registered as NO release rate (pmol x s(-1)) during the plateau of exhalation. Exhaled NO increased steadily over time after nitrate load and a maximum was seen at 120 min (77.0+/-15.2 versus 31.2+/-3.0 pmol x s(-1), p<0.01), whereas no increase was detected in nasal NO levels. Salivary nitrite concentrations increased in parallel; at 120 min there was a four-fold increase compared with baseline (1.56+/-0.44 versus 0.37+/-0.09 mM, p<0.05). The nitrite-reducing conditions in the oral cavity were also manipulated by the use of different mouthwash procedures. The antibacterial agent chlorhexidine acetate (0.2%) decreased NO release by almost 50% (p<0.01) 90 min after nitrate loading and reduced the preload control levels by close to 30% (p<0.05). Sodium bicarbonate (10%) also reduced exhaled NO levels, but to a somewhat lesser extent than chlorhexidine acetate. In conclusion, salivary nitric oxide formation contributes to nitric oxide in exhaled air and a large intake of nitrate-rich foods before the investigation might be misinterpreted as an elevated inflammatory activity in the airways. This potential source of error and the means for avoiding it should be considered in the development of a future standardized method for measurements of exhaled nitric oxide. (+info)
Increased exhaled nitric oxide on days with high outdoor air pollution is of endogenous origin.
(46/20782)
The aim of this study was to assess the effect of outdoor air pollution on exhaled levels of endogenously released nitric oxide. To exclude bias from exogenous NO in the recovered exhaled air (residual NO or NO in dead volume) an experimental design was used that sampled NO of endogenous origin only. The validity of the presented experimental design was established in experiments where subjects were exposed to high levels of exogenous NO (cigarette smoke or 480 microg x m(-3) synthetic NO). Subsequent 1 min breathing and a final inhalation of NO-free air proved to be sufficient to attain pre-exposure values. Using the presented method detecting only endogenous NO in exhaled air, 18 subjects were sampled on 4 separate days with different levels of outdoor air pollution (read as an ambient NO level of 4, 30, 138 and 246 microg x m(-3)). On the 2 days with highest outdoor air pollution, exhaled NO was significantly (p<0.001) increased (67-78%) above the mean baseline value assessed on 4 days with virtually no outdoor air pollution. In conclusion, the level of endogenous nitric oxide in exhaled air is increased on days with high outdoor air pollution. The physiological implications of this findings need to be investigated further. (+info)
Regulation of sympathetic nerve activity in heart failure: a role for nitric oxide and angiotensin II.
(47/20782)
The mechanisms by which sympathetic function is augmented in chronic heart failure (CHF) are not well understood. A previous study from this laboratory (Circ Res. 1998;82:496-502) indicated that blockade of nitric oxide (NO) synthesis resulted in only an increase in renal sympathetic nerve activity (RSNA) when plasma angiotensin II (Ang II) levels were elevated. The present study was undertaken to determine if NO reduces RSNA in rabbits with CHF when Ang II receptors are blocked. Twenty-four New Zealand White rabbits were instrumented with cardiac dimension crystals, a left ventricular pacing lead, and a pacemaker. After pacing at 360 to 380 bpm for approximately 3 weeks, a renal sympathetic nerve electrode and arterial and venous catheters were implanted. Studies were carried out in the conscious state 3 to 7 days after electrode implantation. The effects of a 1-hour infusion of sodium nitroprusside (SNP; 3 microgram . kg-1. min-1) on RSNA and mean arterial pressure (MAP) were determined before and after Ang II blockade with losartan (5 mg/kg) in normal and CHF rabbits. Changes in MAP were readjusted to normal with phenylephrine. Before losartan, SNP evoked a decrease in MAP and an increase in RSNA in both groups that was baroreflex-mediated, because both MAP and RSNA returned to control when phenylephrine was administered. In the normal group, losartan plus SNP caused a reduction in MAP and an increase in RSNA that was 152.6+/-9.8% of control. Phenylephrine returned both MAP and RSNA back to the control levels. However, in the CHF group, losartan plus SNP evoked a smaller change in RSNA for equivalent changes in MAP (117.1+/-4.1% of control). On returning MAP to the control level with phenylephrine, RSNA was reduced to 65.2+/-2.9% of control (P<0. 0001). These data suggest that endogenous Ang II contributes to the sympathoexcitation in the CHF state and that blockade of Ang II receptors plus providing an exogenous source of NO reduces RSNA below the elevated baseline levels. We conclude that both a loss of NO and an increase in Ang II are necessary for sustained increases in sympathetic nerve activity in the CHF state. (+info)
LMR spectroscopy: a new sensitive method for on-line recording of nitric oxide in breath.
(48/20782)
Laser magnetic resonance spectroscopy (LMRS) is a sensitive and isotope-selective technique for determining low concentrations of gaseous free radicals with high time resolution. We used this technique to analyze the nitric oxide (NO) concentration profile while simultaneously measuring the flow and expired volume during several single breathing cycles. Eight healthy, nonallergic volunteers were investigated. An initial NO peak was found in all breathing cycles before the NO concentration dropped to a relatively stable plateau in the late phase of expiration. The nasal NO peak was significantly higher than the oral NO peak. The nasal NO plateau was always higher than the oral NO plateau. The height of the initial nasal and oral NO peak rose with increasing duration of breath hold, whereas the late expiratory NO plateau changed only little for either the nasal or the oral breathing cycles. Our findings demonstrate, in line with other reports using other techniques, that the nose is the primary source for NO within the airways. (+info)