Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Bronchoconstriction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,459 records · Page 81Linked to original sources
PubMed1992

Pretreatment with aerosolized capsaicin potentiates histamine-induced bronchoconstriction in guinea pigs.

The aim of the present study was to examine whether endogenous neuropeptides released from sensory nerves can potentiate airway responsiveness to histamine. Total pulmonary resistance (RL) was measured to assess the bronchial responsiveness to increasing doses of histamine (1.25, 2.5, 5, and 10 micrograms/kg) administered intravenously in 29 anesthetized and artificially ventilated guinea pigs. Pretreatment with aerosolized capsaicin (3 micrograms/ml for 15 to 60 s) 30 min before obtaining the dose-response to histamine significantly potentiated percent increase in RL caused by each dose of intravenously administered histamine. Pretreatment with substance P (0.5 ml/kg of 10(-5) M) administered intravenously also potentiated the airway responsiveness to histamine. As assessed by the amount of extravasation of Monastral blue pigments, both capsaicin aerosol and substance P injected intravenously induced increased vascular permeability in the tracheal mucosa. These findings suggest that endogenous neuropeptides, especially tachykinin such as substance P, can induce airway hyperresponsiveness to nonspecific stimuli and play a possible role in producing airway hyperresponsiveness in bronchial asthma.

Aerosols↗
PubMed1992

Greater effect of inhaled budesonide on adenosine 5'-monophosphate-induced than on sodium-metabisulfite-induced bronchoconstriction in asthma.

Inhaled glucocorticosteroids (GCS) decrease airway responsiveness (AR) in asthma by mechanisms that may involve suppressing airway inflammation and a reduction in the number of inflammatory cells in the airways. To investigate the functional response to a reduction in airway inflammatory cells in asthma, we studied the effects of inhaled budesonide on AR to three different bronchial challenges, adenosine 5'-monophosphate (AMP), which primarily activates mast cells; methacholine (MCh), a direct stimulus, and sodium metabisulfite (MBS), a neural stimulus. In a double-blind randomized crossover manner, with a washout period of 28 days, 12 subjects with mild asthma underwent inhalation challenge with doubling increments of MCh, MBS, and AMP before and after 14 days of treatment with budesonide 0.8 mg twice daily from a multidose dry-powder delivery system (Turbohaler) or matched placebo. Treatment with budesonide reduced AR to MCh and MBS to a similar degree, displacing the dose-response curve of each agonist to the right by 1.17 (95% confidence intervals, 0.34 to 2.00) and 1.06 (0.34 to 1.78) doubling dilutions, respectively, when compared with placebo (p less than 0.01). Budesonide caused an additional and significantly greater reduction in AR to AMP, displacing the dose-response curve to the right by 2.92 (2.12 to 3.72) doubling dilutions when compared with placebo (p less than 0.001) and to the other challenges (p less than 0.01). We conclude that budesonide reduces AR to MCh and MBS by an action common to the effects of both direct and neural stimuli on airway smooth muscle contraction. The greater reduction in AR to AMP suggests that budesonide may have an additional action by reducing airway mast cell numbers and/or function.

Adenosine Monophosphate↗
PubMed1993

Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo.

To examine whether histamine N-methyltransferase (HMT; EC 2.1.1.8) modulates the effects of allergic reaction in vivo, we studied the effects of aerosolized SKF 91488, a specific HMT inhibitor, on the responses to aerosolized histamine in unsensitized guinea pigs and to ovalbumin (OA) antigen inhalation in guinea pigs sensitized to OA. Airway responsiveness was assessed by determining provocation concentrations of histamine and OA aerosols that increased pulmonary resistance to twice the baseline values. SKF 94188 shifted, in a dose-dependent fashion, the dose-response curves to histamine and OA antigen to lower concentrations, and it significantly decreased provocation concentrations of both histamine and OA antigen (p < 0.01). In contrast of SKF 91488, aerosolized aminoguanidine, a specific inhibitor of diamine oxidase (10(-2) M, 90 breaths), did not alter the provocation concentration of histamine (p > 0.20). SKF 91488 (10(-2) M, 90 breaths) caused no significant changes in response to acetylcholine (p > 0.30). HMT activities were observed in the entire airways of the trachea, main bronchi, segmental bronchi and bronchioles, and parenchymal tissues. These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine by antigen challenge on bronchoconstrictor responses in guinea pigs in vivo.

Aerosols↗
PubMed1993

Eosinophils increase lung microvascular permeability via the peroxidase-hydrogen peroxide-halide system. Bronchoconstriction and vasoconstriction unaffected by eosinophil peroxidase inhibition.

Eosinophils have been implicated as effector cells in producing vascular and bronchial constriction and increased microvascular permeability in the lung. Hypohalous acids produced by the eosinophil peroxidase (EPO)-hydrogen peroxide (H2O2)-halide system are stable cytotoxic oxidants. We measured the effects of EPO inhibition in activated eosinophils on vascular permeability, assessed using the capillary filtration coefficient (Kf,c), vascular resistance (Rt,vasc), and airway resistance (Raw) in isolated rat lungs perfused with 5% bovine albumin in Kreb's solution. Eosinophils were harvested by bronchoalveolar lavage of Toxicara canis-infected rats. Infusion of 2 x 10(6) phorbol myristate acetate (PMA)-activated cells produced a 3.3-fold increase in Rt,vasc at 30 min, primarily caused by small vessel constriction, a 2.5-fold increase in Raw at 150 min, and a 1.8-fold increase in Kf,c at 90 min. Inhibition of EPO using 3-amino-1,2,4-triazole (3-AT) prevented the increases in Kf,c, but not those in eosinophil superoxide production, Rt,vasc, or Raw. Addition of 2 mM sodium bromide as preferential EPO substrate caused Kf,c, but not Rt,vasc, or Raw, to increase significantly (2.5-fold) compared with activated eosinophils alone. Thus, the acute changes in microvascular permeability were modulated by activity of the EPO-H2O2-Halide system, but the increased vascular and bronchial resistances were mediated through a different pathway.

Airway Resistance↗
PubMed1993

Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E4 excretion.

Allergen challenge is associated with an increased excretion of urinary leukotriene E4. The source of this increase is unknown, although the lack of effect of inhaled beta-agonists and sodium cromoglycate suggests that airway mast cells may not be involved. We investigated this further using a new and topically potent inhaled glucocorticoid, fluticasone propionate (FP). A group of 10 mild atopic asthmatic subjects (6 males; FEV1 > 60% of predicted; PC20 histamine < or = 8 mg/ml; and on inhaled beta 2-agonists only) were studied before and after a 2-wk period of FP (1,000 micrograms/day) or placebo administered by metered-dose inhalers as two puffs twice per day through a large-volume spacer. Treatments were assigned in a double-blind crossover fashion separated by a 3-wk washout period. The PC20 histamine was measured at the start and end of each treatment when subjects also received a bronchial allergen challenge. Urine was collected for 4 h after allergen challenge for determination of LTE4 using HPLC-RIA, and 2 h later the PC20 histamine measurement was repeated. The 2-wk treatment with FP significantly inhibited both early and late responses to allergen: the maximum % fall in FEV1 during the early (0 to 2 h) and late response (2 to 6 h) was 32.6 +/- 3.4 and 19.6 +/- 5.2, respectively, following placebo versus 19.5 +/- 4.5 and 3.6 +/- 2.6 following FP (both p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed2004

Duration of effect of single-dose inhaled fluticasone propionate on AMP-induced bronchoconstriction.

Airway hyperresponsiveness induced by adenosine-5'-monophosphate (AMP) is regarded as a reliable model for allergic asthma and for the evaluation of anti-asthmatic drugs. Single-dose inhaled corticosteroids (ICS) are known to be protective in this model, but the duration of action of these drugs in this model has never been studied. The duration of ICS protection was determined by administration of single-dose fluticasone propionate (FP; 1,000 micrograms) up to 26 h before AMP challenge. A randomised, double-blind, placebo-controlled, four-way crossover study was performed in 13 mild asthmatics (mean +/- SD predicted forced expiratory volume in one second (FEV1) 98 +/- 7%). Each subject received placebo and FP (at 26, 14 or 2 h prior to the AMP challenge). Furthermore, the marker exhaled nitric oxide (eNO) was studied after administration at these time points to investigate whether eNO also demonstrates the duration of action of ICS. The doubling concentrations difference (DCD) of AMP causing a 20% fall in FEV1, when FP was administered 26, 14 or 2 h prior to challenge, was significantly increased as compared with placebo: DCD (95% confidence interval) at 26 h, 0.73 (0.20-1.26), p = 0.008; 14 h, 1.50 (0.99-2.01), p < 0.001; and 2 h, 2.89 (2.37-3.40), p < 0.001. However, eNO was not significantly affected at these time points. In conclusion, a single dose of 1,000 micrograms inhaled fluticasone propionate protects against adenosine-5'-monophosphate airway hyperresponsiveness up to 26 h after dosing. This study suggests that adenosine-5'-monophosphate challenge can be used as a sensitive marker to study the duration of action of inhaled corticosteroids.

Adenosine Monophosphate↗
PubMed2006

Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen.

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested. Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia. Trypsin, added to the airway lumen (300 microg x mL(-1)), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR1, PAR2 or PAR3 were without effect, but PAR4 AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N(omega)-nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR4 AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR4 AP (but not PAR2 AP) relaxed carbachol-toned airways after <3 min. The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.

Analysis of Variance↗
PubMed1994

Time-limited protective effect of inhaled frusemide against aspirin-induced bronchoconstriction in aspirin-sensitive asthmatics.

Inhaled frusemide effectively prevents the bronchial obstructive response to allergens and to a number of nonallergic stimuli. In most of the experimental models in which it has been tested, the protective effect of frusemide has been evaluated for only a short time after administration. In aspirin-sensitive patients, acetylsalicylic acid causes an asthmatic reaction which typically lasts for 2 h or more after exposure. We investigated the presence and duration of the protective effect of inhaled frusemide against the bronchial response to aspirin in sensitive patients, using a specific inhalation challenge with lysine acetylsalicylate (LASA). In the first study, eight subjects with aspirin-asthma underwent two bronchial challenges with a single dose of lysine acetylsalicylate administered through a jet nebulizer, after treatment with 40 mg inhaled frusemide or placebo, according to a randomized, double-blind protocol. Forced expiratory volume in one second (FEV1) was monitored for 120 min after challenge. In the second study in eight patients, the protocol was modified by the use of a dosimeter for delivery of lysine acetylsalicylate, by reducing the dose of lysine acetylsalicylate to avoid intense reactions, and by extending the follow-up to 4 h. In the first study, after placebo, FEV1 gradually decreased, reaching a maximum decrement of 39 +/- 3% at 120min. Inhaled frusemide exerted a significant protection at all time-points, although this activity appeared to decrease with time. In the second study, after placebo, inhaled lysine acetylsalicylate caused a gradual decrease in FEV1, which reached a maximum decrement at 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1996

Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs.

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.

Allergens↗
PubMed2006

Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice.

BACKGROUND: Previous genetic analysis has shown that a deletion in the complement component 5 gene-coding region renders mice more susceptible to allergen-induced airway hyperresponsiveness (AHR) due to reduced IL-12 production. We investigated the role of complement in a murine model of asthma-like pulmonary inflammation. METHODS: In order to evaluate the role of complement B10 mice either sufficient or deficient in C5 were studied. Both groups of mice immunized and challenged with a house dust extract (HDE) containing high levels of cockroach allergens. Airways hyper-reactivity was determined with whole-body plesthysmography. Bronchoalveolar lavage (BAL) was performed to determine pulmonary cellular recruitment and measure inflammatory mediators. Lung homogenates were assayed for mediators and plasma levels of IgE determined. Pulmonary histology was also evaluated. RESULTS: C5-deficient mice showed enhanced AHR to methylcholine challenge, 474% and 91% increase above baseline Penh in C5-deficient and C5-sufficient mice respectively, p < 0.001. IL-12 levels in the lung homogenate (LH) were only slightly reduced and BAL IL-12 was comparable in C5-sufficient and C5-deficient mice. However, C5-deficient mice had significantly higher cysteinyl-leukotriene levels in the BAL fluid, 1913 +/- 246 pg/ml in C5d and 756 +/- 232 pg/ml in C5-sufficient, p = 0.003. CONCLUSION: These data demonstrate that C5-deficient mice show enhanced AHR due to increased production of cysteinyl-leukotrienes.

Acetates↗
PubMed2006

Development of bronchoconstriction after administration of muscle relaxants in rabbits with normal or hyperreactive airways.

Neuromuscular blocking drugs can induce intraoperative bronchospasm. We characterized the magnitude and the temporal profile of the constriction in normal or in hyperresponsive airways after injections of neuromuscular blocking drugs. Respiratory system impedance (Zrs) was measured continuously over a 90-s apneic period in naïve and rabbits sensitized to allergens by ovalbumin. Fifteen s after the start of Zrs recordings, succinylcholine, mivacurium, or pipecuronium was administered in random order. Zrs was then also recorded during the administration of increasing doses of exogenous histamine. To monitor the changes in the airway mechanics during these maneuvers, Zrs was averaged for 2-s time windows, and the airway resistance (Raw) was determined by model fitting. The increases in Raw were significantly larger in the sensitized rabbits than in the naïve animals. The largest increases in Raw and the maximum rate of change in Raw were obtained for succinylcholine (146% +/- 29% and 0.80 +/- 0.12 cm H2O/L, respectively) and mivacurium (80% +/- 25% and 0.71 +/- 0.13 cm H2O/L) and the smallest were obtained for pipecuronium (40% +/- 12% and 0.41 +/- 0.04 cm H2O/L). Allergic sensitization leads to severe and rapidly developing bronchospasm after administrations of mivacurium or succinylcholine. These deleterious side effects should be considered when succinylcholine or mivacurium is administered in the presence of bronchial hyperreactivity.

Airway Resistance↗
PubMedDate not supplied

Effects of saiboku-to on dual-phase bronchoconstriction in asthmatic guinea pigs.

In recent years, bronchial asthma has come to be regarded pathologically as a chronic inflammatory disease of the respiratory tract. Inhalational steroids and antiinflammatory drugs are recognized as being effective against bronchial asthma. In this study, the effects of Saiboku-to, a Chinese herbal (Kampo) formulation, were investigated on asthmatic guinea pigs sensitized to ovalbumin (OA). Following 7-day administration of Saiboku-to (500 micrograms/kg), the late asthmatic response (LAR) to an antigen challenge was found to be inhibited. The number of eosinophils in fluid obtained by bronchoalveolar lavage (BAL) 4 h after antigen challenge was decreased while the infiltration of eosinophils and T-lymphocytes into the lung parenchyma was inhibited. These findings suggest that Saiboku-to has the potential to become a useful drug in the treatment of bronchial asthma.

Animals↗
PubMed1991

Terfenadine effect on the bronchoconstriction, dermal response, and leukopenia induced by platelet-activating factor.

We have investigated the protective effect of oral terfenadine, a H1 antagonist, on the dermal and pulmonary response, and changes of circulating WBCs to injected and inhaled platelet activating factor. Nine men with mild asthma participated in a double-blind, crossover study using terfenadine, 120 mg, or placebo. Three hours after administration of study drug, pulmonary function was measured, and a PAF challenge was performed. Skin test to histamine and PAF was performed prior to study drug, and 2.5 hours after drug. Circulating WBC count was determined prior to PAF inhalation and during the PAF challenge. There was a significant improvement in pulmonary function on terfenadine. Terfenadine significantly inhibited the wheal and flare response to histamine and the flare response to injected PAF. Terfenadine did not have an effect on the change in circulating WBC count or the change in pulmonary function to inhaled PAF. These results suggest a limited role for endogenous histamine for the effects of PAF.

Asthma↗
PubMed1995

Airway wall liquid. Sources and role as an amplifier of bronchoconstriction.

Airway liquid balance in asthma is largely determined by active plasma exudation from tracheobronchial microvessels into the interstitial spaces of the mucosa, submucosa, and/or adventitia, and from there into the luminal space. This exuded plasma is rich in proteins and cell mediators capable of initiating several events, including activation of sensory neural pathways, plasma protein cleavage, inflammatory cell recruitment, and inhibition of surfactant function. It can act to amplify the bronchoconstrictor response by increasing mucosal and/or submucosal thickness, altering mechanical properties of airway wall compartments, decoupling the airway wall from parenchymal attachments, filling airway interstices, and by creating an additional inward force because of surface tension, resulting in further airway constriction and possibly closure and thereby significantly increasing airways resistance.

Animals↗