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PubMed2006

Effect of ciclesonide dose and duration of therapy on exercise-induced bronchoconstriction in patients with asthma.

BACKGROUND: Inhaled corticosteroid therapy improves exercise symptoms in asthmatic subjects. OBJECTIVE: We sought to evaluate exercise-induced bronchoconstriction (EIB) as a method of determining the dose and time responses of inhaled corticosteroid therapy. METHODS: In this double-blind, randomized, cross-over study with 2 parallel arms, 4 doses of inhaled ciclesonide (40 microg and 160 microg or 80 microg and 320 microg) were compared over 3 weeks of treatment. Twenty-six asthmatic subjects (age range, 14-27 years) with baseline FEV1 values of greater than 70% of predicted value were enrolled. The primary outcome was the maximum percentage decrease in FEV1 after standardized exercise challenge. RESULTS: After 1 week of therapy, the mean +/- SEM reduction in maximum decrease in FEV1 in the ciclesonide 40-microg/80-microg dose group was 9% +/- 2.6% (95% CI, 3.9% to 14%), with no additional reduction thereafter. In the ciclesonide 160-microg/320-microg dose group, there was an 8.7% +/- 2.5% (95% CI, 3.7% to 13.7%) reduction in maximum decrease in FEV1 after week 1, which continued in a linear fashion during subsequent weeks of treatment. No difference was found between the 2 treatment arms in the temporal response of EIB to ciclesonide treatment. The maximum percentage attenuation in EIB achieved was 51.1% +/- 7.9%, which was achieved by using the 320-microg dose after 3 weeks of treatment. CONCLUSIONS: A significant improvement in EIB was demonstrated for all doses of ciclesonide. Use of 160 microg/320 microg of ciclesonide resulted in a continuing improvement in FEV1 with time, and no plateau was seen in protective effect during 3 weeks of treatment. CLINICAL IMPLICATIONS: Attenuation in exercise-induced decrease can be seen as early as after 1 week of therapy with inhaled ciclesonide at doses greater than 40 microg. However, maximal attenuation in exercise response continues to increase at doses greater than or equal to 200 microg, even after 3 weeks of therapy.

Administration, Inhalation↗
PubMed2004

Prevention of bronchoconstriction in sensitized guinea pigs: efficacy of common prophylactic drugs.

Efficacy of beta2-agonists (B2), anticholinergics, corticosteroids, anti-inflammatory drugs or antihistamines against methacholine, histamine, or allergen-induced lung constriction was tested in ovalbumin sensitized guinea pigs. Airway resistance (Raw) and parenchymal damping (G) and elastance (H) were determined from low-frequency forced oscillatory input impedance (ZL). ZL was measured under control conditions, during iv infusions of methacholine, and following iv boluses of histamine or ovalbumin. In decreasing potency, ipratropium, salmeterol, fluticasone or cromoglycate reduced the methacholine-induced increases in Raw and G. Only antihistamines had any effects on the histamine-induced increased in Raw, G, and H. The ovalbumin-induced increases in Raw, G and H in the control animals (120 +/- 90%, 201 +/- 126%, 86 +/- 71%) were markedly reduced by pretreatments with antihistamines (18 +/- 11%, 13 +/- 9%, 3+/- 3%) and cromoglycate (29 +/- 13%, 35 +/- 22%, 18 +/- 10%). Bronchoconstriction induced by muscarinic receptor stimulation is inhibited by anticholinergic, anti-inflammatory or beta2-agonist pretreatment; antihistaminic or anti-inflammatory premedication is beneficial if the release of histamine via an exposure to allergen is responsible for the fall in lung function.

Adrenergic Agonists↗
PubMed2006

Differentiation between the sensory and affective aspects of histamine-induced bronchoconstriction in asthma.

Respiratory symptom perception research has focused mainly on respiratory sensations. Because dyspnea is multidimensional, affective aspects should be investigated. Patients with asthma (N=25) underwent a histamine provocation until a 20% fall in forced expiratory volume in 1s (FEV(1)). After each dose level, 6 symptoms of dyspnea intensity and 6 symptoms of dyspnea affectivity were rated. Individual perceptual sensitivity was determined by calculating the linear slope between the fall in FEV(1) and the increase in the total symptom score, and for affective and sensory symptoms separately [Bijl-Hofland, Folgering, van den Hoogen, et al. Perception of bronchoconstriction in asthma patients measured during histamine challenge test. Eur Respir J 1999;14:1049-54]. Trait anxiety, baseline state anxiety, daily asthma symptoms and catastrophizing during an asthma exacerbation were also assessed. Sensitivity was unrelated to physiological indices of disease severity (i.e., baseline FEV(1) and histamine dose level at 20% fall in FEV(1)), whereas it was positively related to trait anxiety, state anxiety, daily asthma symptoms and catastrophic thinking during an asthma exacerbation in daily life. These relationships were overall much stronger for affective than for sensory symptom slopes. In stepwise multiple regressions, state anxiety was the best predictor of the affective symptom slopes, whereas catastrophic thinking during an asthma exacerbation was the best predictor for the sensory symptom slopes. The differentiation between sensory and affective components of dyspnea adds to the understanding of respiratory symptom perception in asthma.

Adolescent↗
PubMed2003

The role of oxidative stress in bronchoconstriction due to occupational sulfur dioxide exposure.

BACKGROUND: We previously showed that apricot sulfurization workers (ASW) are exposed to high concentrations of SO(2), resulting in an asthma-like syndrome. The aim of this study was to evaluate whether oxidative stress plays a role in the pathogenesis of asthma-like syndrome due to the high concentrations of SO(2) exposure in agricultural environment. METHODS: Serum antioxidant enzyme activities and malondialdehyde (MDA) concentrations, which are markers of lipid peroxidation, and pulmonary function tests (PFT) were measured in 40 volunteer ASW and compared to 20 healthy control subjects. RESULTS: The superoxide dismutase (SOD, 2.2+/-0.6 vs. 3.2+/-0.7 U/ml), glutathione peroxidase (GSH-Px, 0.6+/-0.3 vs. 1.1+/-0.3 U/ml) and catalase (107.6+/-27.4 vs. 152.6+/-14.3 k/l) activities in ASW were significantly (p<0.0001) lower than controls, whereas the malondialdehyde concentration (4.1+/-0.9 vs. 1.9+/-5.3 nmol/l) was higher in ASW (p<0.0001). ASW had significant decreases in pulmonary function parameters after exposure. CONCLUSION: These results show that occupational exposure to high concentrations of SO(2) enhances oxidative stress and lipid peroxidation may be considered as a new mechanism of SO(2)-induced bronchoconstriction.

Adolescent↗
PubMed1998

Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma.

OBJECTIVE: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma. STUDY DESIGN: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV1) > or =70% of the predicted value and a fall in FEV1 > or =20% after exercise on 2 occasions. Patients received montelukast (5-mg chewable tablet) or placebo once daily in the evening for 2 days in crossover fashion (at least 4 days between treatment periods). Standardized exercise challenges were performed 20 to 24 hours after the last dose in each period. End points included area above the postexercise percent fall in FEV1 versus time curve (AAC0-60 min), maximum percent fall in FEV1 from pre-exercise baseline, and time to recovery of FEV1 to within 5% of pre-exercise baseline. RESULTS: Montelukast significantly reduced AAC0-60 min (265 vs 590% x min for montelukast and placebo, respectively, P < or = .05; approximately 59% protection relative to placebo) and the maximum percent fall (18% vs 26% for montelukast and placebo, respectively, P < or = .05). Montelukast treatment resulted in a shorter time to recovery (18 vs 28 minutes for montelukast and placebo, respectively, P = .079). CONCLUSIONS: Montelukast attenuates EIB at the end of the dosing interval in 6- to 14-year-old children with asthma.

Acetates↗
PubMed1998

Do dairy products induce bronchoconstriction in adults with asthma?

BACKGROUND: Dairy products have often been implicated as a cause of exacerbation of asthma, but there is little scientific evidence to support this hypothesis. OBJECTIVE: We sought to determine whether dairy products induce bronchoconstriction in a group of adults with asthma. METHODS: Twenty subjects with asthma (13 women and 7 men) were recruited from respondents who had previously completed a food and asthma questionnaire. Ten subjects perceived that their asthma became worse with ingestion of dairy products (positive perceivers), whereas ten were negative perceivers. None of the subjects had positive skin prick test results with cow's milk. The study was a randomized, cross-over, double-blind, placebo-controlled trial. Subjects complied with a dairy-free diet throughout the study. The active challenge was a single-dose drink equivalent to 300 ml of cow's milk. A positive reaction was defined as a 15% reduction in both FEV1 and peak expiratory flow (PEF) on the active challenge day compared with results obtained at the same time on the placebo day. RESULTS: For both FEV1 and PEF there were no statistically significantly differences in group means between active challenge and placebo challenge, between sequence of administration, or between perceptions. Nine subjects showed FEV1 or PEF changes that were greater than 15% of baseline values: four patients showed changes after both active and placebo treatment; two after treatment with placebo only; and three after active treatment alone. Of the latter group, two subjects showed changes only in PEF, and when one of these subjects underwent a further detailed study, no asthmatic reaction could be demonstrated. CONCLUSION: It is unlikely that dairy products have a specific bronchoconstrictor effect in most patients with asthma, regardless of their perception.

Adolescent↗
PubMed1999

The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness.

BACKGROUND: Single doses of zafirlukast attenuate exercise-induced bronchoconstriction (EIB), but previous studies have not measured zafirlukast's effects after regular dosing or its duration of effect beyond 4 hours. OBJECTIVE: The purpose of this study was to assess the effects of zafirlukast 20 mg and 80 mg twice daily compared with placebo on exercise challenges performed at 2 and 8 hours after the last dose of regular administration. METHODS: Twenty-four adult patients with stable asthma taking beta(2)-agonists, inhaled corticosteroids, or both received treatment with zafirlukast (20 mg and 80 mg) and placebo. The patients were treated twice daily for 14 days in a randomized, double-blind, 3-way cross-over fashion, with a 7-day washout period between each treatment. Exercise challenges were performed at 2 and 8 hours after the morning dose on day 14. FEV(1) was measured before exercise and at set intervals after exercise until it returned to within 7% of its baseline value. RESULTS: Both zafirlukast treatments significantly reduced EIB, as measured by the area under the FEV(1) time curve after the 2-hour (P <.001) and 8-hour (P <.001) exercise challenges and maximum fall in FEV(1) at the 2-hour challenge (P <.001). The comparison at 8 hours between treatments was affected by the unexpected finding that EIB was less in the placebo group after the 8-hour challenge than after the 2-hour challenge, as measured by the within-group change in the maximum fall in FEV(1) (P <.001) and the area under the FEV(1) time curve (P =.0023). CONCLUSION: Regular zafirlukast treatment protects against EIB for at least 8 hours after regular dosing. A refractory period, which may be caused by exercise-induced leukotriene release, may last for up to 6 hours after the initial response to exercise.

Adolescent↗
PubMed2002

A randomized, double-blind, single-dose, crossover clinical trial of the onset and duration of protection from exercise-induced bronchoconstriction by formoterol and albuterol.

BACKGROUND: Inhaled short-acting beta(2)-adrenoceptor agonists are the most commonly used treatment for the prevention of exercise-induced bronchoconstriction (EIB). Formoterol, a long-acting beta(2)-adrenoceptor agonist, has been demonstrated to provide protection from EIB, although the onset and duration of this protection have not been defined. OBJECTIVE: The purpose of this study was to determine the onset and duration of the protective effect of a single dose of inhaled formoterol powder against EIB, comparing them with the effect of a single dose of placebo and albuterol administered via metered-dose inhaler (MDI). METHODS: In this double-dummy, 4-way crossover study, patients received single doses of formoterol (12 and 24 microg) via a powder inhaler, albuterol by MDI (180 microg), and placebo. Exercise challenge tests (ECTs) were conducted at 15 minutes and at 4, 8, and 12 hours postdose. Pulmonary function studies (forced expiratory volume in 1 second [FEV(1)] and peak expiratory flow rate) were performed before and after each exercise challenge. RESULTS: Twenty adolescent and adult patients (mean age, 23.8 years; range, 13-41 years; 9 male, 11 female) with asthma were enrolled in the study, and 17 completed all 4 treatment sequences. Compared with placebo, both doses of formoterol produced significantly greater inhibition of FEV(1) decreases at all time points (P < 0.01). There were no significant differences in efficacy measures between the 2 formoterol doses throughout the study. The exercise-induced decrease in FEV(1) after albuterol treatment was significantly reduced compared with placebo only at 15 minutes after dosing (P < 0.05). Formoterol and albuterol exhibited a similar rapid onset of action (<15 minutes), but formoterol continued to protect patients against EIB for at least 12 hours (P < 0.01), whereas albuterol was no longer clinically effective by the 4-hour ECT. CONCLUSIONS: Formoterol and albuterol, given as single-dose inhalations, both provided protection from EIB within 15 minutes in this group of patients. The bronchoprotection afforded by formoterol lasted up to 12 hours, whereas that of albuterol was no longer significant by 4 hours.

Administration, Inhalation↗
PubMed2000

The alpha3 subtype of the nicotinic acetylcholine receptor is expressed in airway-related neurons of the nucleus tractus solitarius, but is not essential for reflex bronchoconstriction in ferrets.

To assess the role of nicotinic acetylcholine receptors (nACh-R) in the transmission of afferent constricting inputs from bronchopulmonary receptors to the nucleus tractus solitarius (nTS) and in the mediation of reflex airway constriction, we performed a combined immunohistological and functional study. In ferrets, the expression of nAch-R on the nTS neurons activated by histamine stimulation of airway sensory receptors was studied using laser scanning confocal microscopy to co-immunolocalize c-fos encoded protein (cFos) and nACh-R alpha3 subunit. We observed that activation of airway sensory receptors by inhalation of aerosolized histamine, induced cFos expression in a subset of nTS neurons that also expressed the nAch-R alpha3 subtype. Furthermore, activation of nACh-R within the commissural subnucleus by nicotine, increased cholinergic outflow to the airways. These effects were diminished by prior administration of hexamethonium (nACh-R blocker) within the commissural subnucleus of the nTS. However, hexamethonium had no significant effects on airway reflex constrictions induced by lung deflation. These findings indicate that nACh-R are expressed by the nTS neurons receiving inputs from airway sensory receptors, activation of which by nicotine increases cholinergic outflow to the airways, but the nACh-R pathways are not required for reflex bronchoconstriction.

Airway Resistance↗
PubMed1997

Neural reflex-mediated tracheal response during bronchoconstriction induced by ovalbumin antigen in guinea pigs.

1. The biphasic reflex tracheal response (constriction followed by dilatation) occurred during bronchoconstriction induced by inhalation of ovalbumin antigen (OA) in sensitized guinea pigs. 2. The reflex tracheal constriction was largely reduced by atropine, and the dilatation was inhibited by propranolol and N omega-nitro-L-arginine methyl ester (L-NAME). The noradrenaline, adrenaline, cyclic AMP, and cyclic GMP contents in the tracheal segment were significantly higher during reflex tracheal dilatation. 3. These findings suggest that cholinergic nerves may mediate reflex tracheal constriction and that adrenergic and NOergic nerves may mediate the ensuing reflex tracheal dilatation.

Allergens↗
PubMed2003

Hypothetical mechanism of prostaglandin E1-induced bronchoconstriction.

In general, prostaglandin E1 (PGE1) is thought to relax smooth muscles in the airway and to inhibit muscle constriction. We hypothesized that, under the specific conditions, PGE1 induces bronchoconstriction, resulting in the promotion of inflammation. Examples of the specific conditions where this mechanism may occur include cases where patient who are susceptible to inflammation receive a continuous infusion of PGE1 during induced hypotension or during treatment for intraoperatively abnormal hypertension.

Administration, Topical↗
PubMed2003

Respiratory conductance response to a deep inhalation in children with exercise-induced bronchoconstriction.

Airway response to deep inhalation (DI) may provide information relevant to the mechanisms of airway obstruction (AO). The hypothesis examined here is that DI provokes bronchodilation in children during exercise-induced bronchoconstriction (EIB). EIB was attested in 15 children aged 10+/-3 year (mean+/-SD) by a decrease in forced expiratory volume in 1 s (FEV1) > or = 15% from baseline after a free running test. The respiratory resistance was measured by the forced oscillation technique at 12 Hz using a head generator to vary transrespiratory pressure around the head. The airway response to DI was estimated by the effect on respiratory conductance (Grs), calculated as the reciprocal of respiratory resistance in inspiration. During EIB, DI induced a variable but significant increase in Grs, from 0.085+/-0.023 to 0.101+/-0.029 l hPa(-1) s(-1) (P = 0.0003). The post- to pre-DI Grs ratio (1.19+/-0.14) was found to correlate negatively with EIB-induced reduction in FEV1 (P = 0.02), forced vital capacity (FVC) (P = 0.01) but not FEV1/FVC, i.e., DI induced more bronchodilation in those children with small EIB associated reduction in FVC. It is concluded that the bronchodilator effect of DI may be demonstrated in children with EIB. It is suggested that the associated small airway closure and lung hyperinflation may contribute to limit this response to DI.

Adolescent↗
PubMed1990

Reproducibility of methacholine induced bronchoconstriction in healthy subjects: the use of area under the expiratory flow-volume curve to express results.

The usefulness of the pulmonary function variable, area under the expiratory flow-volume curve (AEFV), in methacholine provocation (MP) studies in normal subjects was evaluated. The baseline coefficients of variation (CV), maximal fall from post-saline values (MAX) and dose-response slope [DRS = maximal percentage fall in pulmonary function/maximal noncumulative methacholine dose (mumol)] were calculated for AEFV, and were compared to those of forced expiratory volume in one second (FEV1), maximum expiratory flow at 50% (MEF50%) and at 25% (MEF25%). Also the repeatability after 2 and 8 weeks was assessed. The rank order of CVs was FEV1 less than AEFV less than MEF50% approximately MEF25% all differences, except MEF50% vs. MEF25%, being significant (P less than 0.05). The order of sensitivities (estimated with MAX and DRS) was FEV1 less than AEFV less than MEF50% less than MEF25%. Again, all differences were significant (AEFV vs. MEF50% P less than 0.01, others P less than 0.001). After two weeks the correlation coefficients for MAX- and DRS-values of AEFV were 0.84 and 0.94 (P less than 0.001), respectively. After an eight week period the correlations were still high, 0.86 and 0.92 (P less than 0.001), respectively, but the actual MAX- and DRS-values tended to be smaller than eight weeks before. The repeatability of MAX of AEFV was not quite as high as that of FEV1. On the other hand, the correlations of DRS-value derived from AEFV were markedly better than those derived from FEV1. In conclusion, MP in normal subjects is well repeatable at least within two weeks, but after an eight week period disturbing factors may intervene reducing repeatability. AEFV can be considered at least as good a pulmonary function variable as FEV1 in demonstrating bronchoconstriction during MPs in normal subjects, and it might even be a better variable to obtain DRS-values than other variables tested.

Adult↗
PubMed2001

Protective effect of a PAR2-activating peptide on histamine-induced bronchoconstriction in guinea-pig.

1. Protease activated receptor-2 (PAR2) is a seven transmembrane domain G protein coupled receptor proteolytically activated. PAR2, together with other PARs, can be also activated by peptides mimicking the sequence of the receptor tethered ligand. We have evaluated the effect of systemic administration of a peptide activating PAR2 (PAR2-AP, SLIGRL) on histamine-induced increase in lung resistances in the guinea-pig. 2. Intravenous administration of PAR2-AP (1 mg kg(-1)) significantly inhibited histamine-induced increase in lung resistance in a time-dependent fashion that was not abolished by indomethacin or vagotomy. 3. Bronchoprotective effect of PAR2-AP was not reversed by the cyclo-oxygenase inhibitor, indomethacin, the nitric oxide synthetase inhibitor, L-NAME, nor by the non-selective beta-antagonist, propranolol. 4. Indomethacin augmented the bronchoconstriction to histamine which was inhibited by PAR2-AP. Furthermore, in vagotomized animals, the bronchial hyper-responsiveness to histamine was significantly reduced, and in these circumstances, PAR2-AP still retained the capacity to provide bronchoprotection against histamine. 5. PAR2-AP also produced a modest reduction in histamine-induced protein leakage in trachea and upper bronchi. 6. Our results indicated that PAR2 might have a bronchoprotective role in the guinea-pig in vivo independent of prostaglandin or nitric oxide release.

Analysis of Variance↗
PubMed2005

Dietary polyunsaturated fatty acids in asthma- and exercise-induced bronchoconstriction.

Despite progress that has been made in the treatment of asthma, the prevalence and burden of this disease has continued to increase. While pharmacological treatment of asthma is usually highly effective, medications may have significant side effects or exhibit tachyphylaxis. Alternative therapies for treatment that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. Ecological and temporal data suggest that dietary factors may have a role in recent increases in the prevalence of asthma. A possible contributing factor to the increased incidence of asthma in Western societies may be the consumption of a proinflammatory diet. In the typical Western diet, 20- to 25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which promotes the release of proinflammatory arachidonic acid metabolites (leukotrienes and prostanoids). This review will analyze the evidence for the health effects of n-3 PUFA in asthma- and exercise-induced bronchoconstriction (EIB). While clinical data evaluating the effect of omega-3 fatty acid supplementation in asthma has been equivocal, it has recently been shown that fish oil supplementation, rich in n-3 PUFA, reduces airway narrowing, medication use, and proinflammatory mediator generation in nonatopic elite athletes with EIB. These findings are provocative and suggest that dietary fish oil supplementation may be a viable treatment modality and/or adjunct therapy in asthma and EIB.

Airway Resistance↗
PubMed1996

Influence of treatment with beclomethasone, cromoglycate and theophylline on perception of bronchoconstriction in patients with bronchial asthma.

1. Perception of asthma by patients can be assessed from the relationship between symptom scores and peak expiratory flows. This study was designed to investigate the possibility that medication can affect perception of the sensation of asthma independently of changes in lung function. 2. Twelve subjects whose asthma was inadequately controlled by inhaled bronchodilator alone were studied during four different drug treatments over 3 months. Subjective self-assessment of asthma was scored on a 10 cm visual analogue scale and followed by three consecutive measurements of peak expiratory flow, using a coded electronic peak flow meter. This was recorded not less than three times daily on diary cards. Observations were recorded during the second week of each of four treatments: (i) a run-in period using only inhaled salbutamol as required, (ii) inhaled beclomethasone, (iii) inhaled cromoglycate and (iv) oral theophylline at a dose adjusted to achieve blood levels of 10-20 mg/l. Inhaled salbutamol was permitted during the other treatments as required. Changes in the slope and position of the regression lines of asthma scores on PEF were used to measure changes in perception of asthma on each treatment. Dynamic lung volumes were measured in the clinic before the study and after each treatment period. 3. In the group as a whole, theophylline improved lung function (mean peak flow and dynamic lung volumes) without affecting mean visual analogue scores, beclomethasone improved mean visual analogue scores with much less effect on lung function, while cromoglycate had a small though consistent effect on both. 4. Perception of asthma, measured by the relationship between peak flow rate and visual analogue scores, was unaffected by cromoglycate. On theophylline, perception of asthma was heightened in five subjects despite a definite improvement in their peak flow. On beclomethasone, perception of asthma was reduced in most subjects, often with no discernible improvement in mean peak flow or dynamic spirometry. 5. Perception of bronchoconstriction in asthma can be affected by drugs independently of control of the condition. Theophylline may produce a paradoxical increase in awareness of asthma in some individuals. With beclomethasone therapy a reduction in symptoms of asthma may occur without any improvement in tests of air flow.

Adult↗
PubMed1997

Water-soluble fullerene derivatives attenuate exsanguination-induced bronchoconstriction of guinea-pigs.

1. This study investigated the effects of increased antioxidants (administration of water-soluble fullerenol-1 and pre-exposure to chronic hypoxia) as well as an iron-chelating agent (deferoxamine) on exsanguination-induced noncholinergic airway constriction in guinea-pigs. 2. Fullerenol-1 usually did not cause significant alteration in respiratory function (lung volumes, dynamic respiratory compliance, maximal expiratory flow at 50% total lung capacity (Vmax50), and forced expiratory flow at 0.1 s (FEV 0.1) at low (200 micrograms kg-1) or at high doses (2 mg kg-1), except that it produced a slight bronchial constricting action (decreases in both Vmax 50 and FEV 0.1) at high doses (2 mg kg-1) via intratracheal instillation. 3. Beginning 15 min after exsanguination, there was a marked temporal decrease in FEV 0.1, indicating a gradual increase in airway constriction with time. 4. Administration of either fullerenol-1 or deferoxamine, or pre-exposure to chronic hypoxia significantly ameliorated the exsanguination-induced bronchoconstriction. The results provide evidence that oxygen radicals play an important role in exsanguination-induced airway constriction. 5. The significant effects of the increased antioxidants and deferoxamine,however, cannot be explained by the alteration in either tracheal neutral endopeptidase activity or lung tissue substance P level.

Animals↗
PubMed1998

Tachykinins in propranolol-augmented, hyperpnoea-induced bronchoconstriction in Taida guinea-pigs: effects of dimethylthiourea.

1. The present authors recently found that a marked hyperpnoea-induced bronchoconstriction (HIB) only occurred in guinea-pigs after treatment with propranolol, a non-selective beta-adrenoceptor antagonist. This study investigated tachykinin-dependent and antioxidant-modulated mechanisms for this propranolol-augmented HIB. 2. Guinea-pigs were pre-treated with an antioxidant, dimethylthiourea (DMTU), or saline for 3 days. On the day of study, each animal was given a dose of propranolol (0.5 mg kg(-1)), then the airway function was examined in the anaesthetized-paralysed animal before, during and after hyperpnoea with a dry 95% O2:5% CO2 gas mixture. Tracheal neutral endopeptidase (NEP) activity and plasma substance P (SP) level were measured after functional study. 3. In the presence of propranolol, HIB was augmented, and was found to be associated with decreased NEP activity and an increased plasma SP level. The augmented HIB was attenuated by DMTU. 4. Therefore, the present results suggest that propranolol-augmented HIB is tachykinin-dependent and is modulated by DMTU.

Adrenergic beta-Antagonists↗