Bradykinin-induced bronchospasm in the rat in vivo: a role for nitric oxide modulation.
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)
Reduction of exercise-induced asthma in children by short, repeated warm ups.
AIM: To study the effect of a warm up schedule on exercise-induced asthma in asthmatic children to enable them to engage in asthmogenic activities. METHOD: In the first study, peak flows during and after three short, repeated warm up schedules (SRWU 1, 2, and 3), identical in form but differing in intensity, were compared in 16 asthmatic children. In the second study the efficiency of the best of these SRWU schedules was tested on 30 young asthmatic children. Children performed on different days a 7 minute run alone (EX1) or the same run after an SRWU (EX2). RESULTS: The second study showed that for most children (24/30) the fall in peak flow after EX2 was less than that after EX1. The percentage fall in peak flow after EX2 was significantly correlated with the percentage change in peak flow induced by SRWU2 (r = 0.68). The children were divided into three subgroups according to the change in peak flow after SRWU2: (G1: increase in peak flow; G2: < 15% fall in peak flow; G3: > 15% fall in peak flow). Only the children in the G3 subgroup did not show any gain in peak flow after EX2 compared with EX1. CONCLUSION: The alteration in peak flow at the end of the SRWU period was a good predictor of the occurrence of bronchoconstriction after EX2. An SRWU reduced the decrease in peak flow for most of the children (24/30) in this series, thus reducing subsequent post-exercise deep bronchoconstriction. (+info)
Reactive airways dysfunction and systemic complaints after mass exposure to bromine.
Occasionally children are the victims of mass poisoning from an environmental contaminant that occurs due to an unexpected common point source of exposure. In many cases the contaminant is a widely used chemical generally considered to be safe. In the following case, members of a sports team visiting a community for an athletic event were exposed to chemicals while staying at a local motel. Bromine-based sanitizing agents and other chemicals such as hydrochloric acid, which were used in excess in the motel's swimming pool, may have accounted for symptoms experienced by the boy reported here and at least 16 other adolescents. Samples of pool water contained excess bromine (8.2 microg/mL; ideal pool bromine concentration is 2-4 microg/mL). Symptoms and signs attributable to bromine toxicity included irritative skin rashes; eye, nose, and throat irritation; bronchospasm; reduced exercise tolerance; fatigue; headache; gastrointestinal disturbances; and myalgias. While most of the victims recovered within a few days, the index case and several other adolescents had persistent or recurrent symptoms lasting weeks to months after the exposure. (+info)
Regulation of baseline cholinergic tone in guinea-pig airway smooth muscle.
1. We quantified baseline cholinergic tone in the trachealis of mechanically ventilated guinea-pigs and determined the influence of vagal afferent nerve activity on this parasympathetic tone. 2. There was a substantial amount of baseline cholinergic tone in the guinea-pig trachea, eliciting contractions of the trachealis that averaged 24.6 +/- 3.5 % (mean +/- s.e.m.) of the maximum attainable contraction. This tone was essentially abolished by vagotomy or ganglionic blockade, suggesting that it was dependent upon on-going pre-ganglionic input arising from the central nervous system. 3. Cholinergic tone in the trachealis could be markedly and rapidly altered (either increased or decreased) by changes in ventilation (e. g. cessation of ventilation; hyperpnoea; slow, deep breathing) and by lung distention (via positive end-expiratory pressure). These effects were not accompanied by marked alterations in blood gases and were abolished by vagotomy or atropine. By contrast, tachykinin receptor antagonists, which abolished capsaicin-induced bronchospasm, were without effect on baseline cholinergic tone. This and other evidence suggests that capsaicin-sensitive nerves have little if any influence on baseline parasympathetic tone. Likewise, while activation of afferent nerves innervating the larynx can alter airway parasympathetic nerve activity, transection of the superior laryngeal nerves was without effect on baseline cholinergic tone. 4. Cutting the vagus nerves caudal to the recurrent laryngeal nerves, thus leaving the preganglionic parasympathetic innervation of the trachealis intact but disrupting all afferent nerves innervating the lungs and intrapulmonary airways, abolished baseline cholinergic tone in the trachea. Sham vagotomy or cutting the vagi caudal to the lungs did not reduce baseline cholinergic tone. 5. The results indicate that baseline airway cholinergic nerve activity is necessarily dependent upon afferent nerve activity arising from the intrapulmonary airways and lungs. More specifically, the data are consistent with the hypothesis that on-going activity arising from the nerve terminals of intrapulmonary rapidly adapting receptors determines the level of baseline airway cholinergic tone. (+info)
Bronchodilating effects of bambuterol on bronchoconstriction in guinea pigs.
AIM: To study the effects of bambuterol (Bam) on bronchoconstriction in guinea pigs. METHODS: Bronchospasm induced by histamine aerosol, lung resistance (RL) and dynamic lung compliance (Cdyn) changes induced by ovalbumin aerosol in vivo, isolated resting lung parenchyma strips, and carbamylcholine-induced tracheal constriction in vitro in guinea pig were investigated. RESULTS: Bam dose-dependently prolonged the time to histamine-induced collapse, ED50 values (95% confidence limits) of Bam intragastric gavage (i.g.) after 1 h, 4 h, and 24 h were 0.74 (0.60-0.91), 0.75 (0.61-0.91) and 1.00 (0.77-1.30) mg.kg-1, respectively. Bam 2 or 10 mg.kg-1 i.g. 2 h before ovalbumin aerosol partly or almost completely inhibited bronchial challenge of ovalbumin-induced change of RL and Cdyn. Bam 0.1-1.0 mumol.L-1 gave a weak relaxation on isolated tracheal strips induced by carbamylcholine and failed to relax the isolated resting lung parenchyma strips in guinea pig. CONCLUSION: Bam showed a long-acting bronchodilation by its slow metabolism in vivo. (+info)
Monosodium glutamate and asthma.
Allen et al. (1987) conducted oral monosodium glutamate (MSG) challenges with 32 asthmatic volunteers and reported that 14 reacted to MSG. Another study by Moneret-Vautrin (1987) also reported MSG-induced asthma attacks in 2 of 30 asthmatic patients. Four additional studies have been conducted and none has confirmed the results of the above authors. These studies, by Schwartzstein et al. (1987), Germano (1991), Woods et al. (1998) and Woessner et al. (1999), challenged a total of 45 patients who gave a history of asthma attacks in oriental restaurants. None of these patients experienced asthmatic reactions after ingesting MSG (one-sided confidence interval of 0-0.066). Another 109 asthmatic patients, without a history of asthma in oriental restaurants, also did not react to ingestion of MSG (one-sided confidence interval of 0-0.027). With a confidence interval < 0.05 there is a >95% probability that MSG history-negative asthmatic patients are not sensitive to MSG. For the MSG history-positive asthmatics, 45 patients, in well-performed studies, underwent negative challenges to MSG, contrasting with two studies reporting positive challenges. Allen et al. (1987) and Moneret-Vautrin (1987), who reported positive MSG challenge results, performed studies with the following characteristics: 1) single blinded, conducted after discontinuing essential antiasthma medications; 2) used effort-dependent peak expiratory flow rate measurement of lung function; 3) added AM bronchodilators in some patients; 4) ignored wandering baselines on the placebo challenge days; and 5) conducted some challenges in the AM and some at night. In summary, the existence of MSG-induced asthma, even in history-positive patients, has not been established conclusively. (+info)
Leukotriene-receptor antagonists. Role in asthma management.
OBJECTIVE: To examine the role of leukotriene-receptor antagonists (LTRAs) in management of asthma. QUALITY OF EVIDENCE: Most data were derived from randomized, double-blind, controlled trials. MAIN MESSAGE: Leukotrienes appear to have an important role in the pathophysiology of asthma, including airway inflammation. Leukotriene-receptor antagonists are effective in improving asthma control end points, such as allergen, ASA, and exercise challenge, in clinical models of asthma. In chronic asthma, LTRA administration reduces asthma symptoms and rescue beta 2-agonist use, changes that are paralleled by improvements in lung function. Both zafirlukast and montelukast decrease circulating levels of eosinophils and could have other useful anti-inflammatory properties. Administration of LTRAs allows doses of inhaled corticosteroids to be reduced. Currently available LTRAs are free of serious side effects and are available as oral formulations. CONCLUSIONS: Leukotriene-receptor antagonists belong to a new class of asthma medication. While inhaled corticosteroids remain first-line therapy for managing chronic asthma, LTRAs should be considered for patients with ASA-sensitive asthma; as adjunct therapy when low to moderate doses of inhaled steroid alone provide incomplete control; or as adjunct therapy to allow reduction in doses of inhaled corticosteroids. (+info)
Effects of fenoterol and ipratropium on respiratory resistance of asthmatics after tracheal intubation.
We have studied the effects of a beta-agonist, fenoterol, and a cholinergic antagonist, ipratropium, on post-intubation total respiratory system resistance (Rrs) in asthmatics who developed increased Rrs after tracheal intubation. Sixteen stable asthmatics in whom Rrs increased after intubation were allocated randomly to receive either 10 puffs of fenoterol (group F) or 10 puffs of ipratropium (group IB) via a metered dose inhaler 5 min after intubation. Anaesthesia was induced and maintained with propofol i.v. Rrs was recorded before treatment and again 5, 15 and 30 min after treatment. Rrs decreased significantly from pretreatment values by mean 53 (SD 8)%, 53 (7)% and 58 (6)% at 5, 15 and 30 min, respectively, in group F, but declined by only 12 (6)%, 15 (4)% and 17 (5)% in group IB. At all times after treatment, patients in the fenoterol group had significantly lower Rrs values than those in the ipratropium group. We conclude that increased Rrs after tracheal intubation in asthmatics can be reduced effectively by treatment with fenoterol. A secondary finding of our study was that even after induction of anaesthesia with propofol, patients with a history of asthma may develop high Rrs. (+info)