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 955 records · Page 53Linked to original sources
PubMed2006

Applicability of interrupter resistance measurements for evaluation of exercise-induced bronchoconstriction in children.

The interrupter technique is a noninvasive method for measuring air-flow resistance during tidal breathing. This method requires minimal cooperation, and is therefore promising for use in uncooperative children. The aim of this study was to evaluate applicability interrupter resistance (Rint) measurements in the assessment of exercise-induced bronchoconstriction (EIB). Fifty children aged 5-12 years with mild to moderate asthma were tested by exercise challenge, consisting of free outdoor running for 6 min at 80-90% of maximal predicted heart rate for age. Rint, forced expiratory volume in 1 sec (FEV1), and peak expiratory flow (PEF) were measured before and 10 min after exercise. EIB was defined as a fall of 10% or more in FEV1 after exercise. The repeatability of Rint was assessed, and its response to exercise challenge was compared with current standardized methods. The mean intermeasurement coefficient of variation was 4.6% (SD, +/- 3.0%), and the repeatability coefficient was 0.056 kPa/l/sec. Eighteen (36%) of the 50 children had EIB after exercise challenge test. The area under the receiver-operating characteristic (ROC) curve was 0.953 (95% confidence interval, 0.853-0.992; P < 0.001), and the optimal Rint cutoff value was 15.2%, producing a sensitivity of 88.9% and a specificity of 96.9%. The positive and negative predictive values were 94.1% and 93.9%, respectively. The kappa value between FEV1 and Rint was 0.83. The repeatability of Rint measurements was good, and the results of exercise challenge tests using Rint measurements have excellent agreement with the current standardized methods to detect EIB. Considering that only minimal comprehension and coordination are needed without forced breathing technique, the Rint measurement can provide a useful alternative for assessment of EIB in children unable to perform reliable spirometry.

Airway Resistance↗
PubMed2006

Eosinophils play a major role in the severity of exercise-induced bronchoconstriction in children with asthma.

Exercise-induced bronchoconstriction (EIB) was associated with eosinophilic airway inflammation, bronchial hyperresponsiveness (BHR), atopy and airway obstruction. To understand the pathogenesis of EIB, we determine whether eosinophil is more related to the mechanism of EIB than atopy, BHR and airway obstruction. This study comprised 268 asthmatic children who underwent lung function test, methacholine challenge test, exercise challenge test, and blood tests for total IgE levels and total eosinophil counts (TEC). Urine eosinophil protein X (EPX) levels after exercise were measured by using ELISA method. EIB was observed in 195 of 268 asthmatics (72.8%). Asthmatics with EIB showed significantly increased TEC (P < 0.01) and decreased log PC(20) as compared with asthmatics without EIB. Maximal percent fall in FEV(1) after exercise was significantly correlated with TEC, log IgE, FEF(25-75%), log PC(20) (P < 0.001, respectively) and FEV(1) (P = 0.013). When the same study was carried out in nonatopic asthmatics, those with EIB showed significantly increased TEC (P = 0.01) compared with those without EIB; however, log PC(20), FEV(1), and FEF(25-75%) showed no significant differences between the two groups of nonatopic asthmatics. In addition, there was a significant correlation between the severity of EIB and TEC in nonatopic asthmatics. Urine EPX/Cr levels after exercise were correlated with the severity of EIB (r = 0.238, P = 0.014). Blood eosinophils and urine EPX/Cr after exercise correlate significantly with the maximal percent fall in FEV(1) after exercise, therefore EIB may reflect a state of eosinophilic inflammation in the airway of asthmatic children.

Adolescent↗
PubMed2006

Dalhousie dyspnea scales: Pictorial scales to measure dyspnea during induced bronchoconstriction.

The aim of this study was to validate our Dalhousie Dyspnea Scales in children referred for histamine bronchoprovocation challenge. Seventy-four children rated their dyspnea after each FEV(1) measurement following inhalation of doubling histamine concentrations from 0.125 to 8.0 mg/ml by the standard tidal breathing method. Serial FEV(1) and dyspnea rating using the Dalhousie Dyspnea Scales were recorded and Kendall's tau was computed for dyspnea rating versus fall in FEV(1). Subjects were split into those with positive (DeltaFEV(1) >or= 20% with PC(20) <or= 8 mg/ml) or negative histamine challenge test. During histamine inhalation, dyspnea ratings on each of the subscales rose as FEV(1) fell across subjects, whether or not they were histamine-responsive (main effect), and then fell dramatically following relief of induced obstruction by bronchodilator.The Dalhousie Dyspnea Scales are useful and accurate tools to measure dyspnea due to bronchoconstriction in children.

Administration, Inhalation↗
PubMedDate not supplied

Lung constant-pressure inflation: fluid dynamic factors are the basis of airway overpressure during bronchoconstriction.

Dynamic pressure-volume methods with constant-pressure inflation are frequently used when assessing drug activity in the lungs of small animals where it is difficult to measure airway resistance and dynamic lung compliance. They all employ a ventilator which provides constant volume inflation and a breathing circuit designed to limit the airway pressure: the supply line from the ventilator to the animal is connected through a T-piece to a tube (immersion tube) immersed in a liquid-filled container. The immersion depth of the tube (backpressure) limits the peak inspiratory pressure (PIP). This approach should avoid the PIP within the circuit exceeding the backpressure. However, we have observed that a marked overpressure was generated during histamine-induced bronchoconstriction if a small diameter immersion tube (< 0.4 cm) was used when setting up such a circuit. In vivo as well as in vitro experiments were carried out with glass immersion tubes of different cross-sectional areas (0.3, 0.42 and 0.62 cm). These settings caused a significant difference in the duration of airway resistance changes among groups without affecting the peak overflow. Overpressure was dependent upon several factors: diameter of the immersion tube, tidal volume and ventilatory rate. Theoretical considerations, as well as in vitro and in vivo experiments, indicated that an immersion tube with inner diameter (ID) of 0.6 cm prevented the overpressure in the majority of experimental settings.

Airway Resistance↗
PubMed1999

Cooling-induced bronchoconstriction: the role of ion-pumps and ion-carrier systems.

The mechanism of cold-induced bronchoconstriction is poorly understood. Our previous results show that cooling-induced contractions (CIC) do not involve activation of cell surface receptor systems nor innervation nor Ca2+ uptake. However, the results show that CIC is mainly dependent on intracellular Ca2+ [32]. Isolated tracheal strips and bronchiolar segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue responses during stepwise cooling from 37 to 5 degrees C were examined. Cooling ovine tracheal strips and bronchiolar ring segments to 20 degrees C caused a rapid contraction which decreased slowly until it reached the basal level in approximately 30 min. There is a significant inhibition of 45Ca2+ efflux at 20 degrees C to those incubated at 37 degrees C. This prompted this study whose aim was to determine the role of ion-pump and ion-carrier systems on cooling mechanisms. Inhibition of the Na+/K+ pump with ouabain (10 micrometer) evoked contraction in tracheal and bronchiolar preparations. When cooling was superimposed on this contraction the cooling-induced contractions were reduced in the bronchiolar segments. In the tracheal strips, at temperatures down to 15 degrees C ouabain converted the contractions to a relaxation, but further cooling to 10 and 5 degrees C resulted in contractions that were similar to control at 5 degrees C. Staurosporine, a protein kinase inhibitor (1 micrometer) enhanced CIC in trachea and bronchiole. Vanadate, a Ca2+-ATPase pump inhibitor (1 mm) potentiated CIC in the two preparations. Trifluoperazine and W-7, calmodulin antagonists (10 and 100 micrometer) enhanced CIC in tracheal preparations but not in the bronchiolar segments. Thapsigargin and cyclopiazonic acid (CPA), inhibitors of sarcoplasmic reticulum (SR) Ca2+-ATPase pump (1 and 10 micrometer) potentiated CIC in tracheal but not in bronchiolar preparations. Amiloride, Na+/H+ and Na+/Ca2+ exchange system inhibitor (1 mm) abolished CIC in both trachea and bronchiole. These results show a strong relationship between cooling and the activity of ion transport systems and indicate that CIC is due to inhibition of calcium removal mechanisms as a result of inhibition of these ion-pump and ion carrier systems.

Animals↗
PubMed1999

The beta(2)-agonist salbutamol inhibits bronchoconstriction and leukotriene D(4) synthesis after dry gas hyperpnea in the guinea-pig.

Isocapnic dry gas hyperpnea-induced bronchoconstriction (HIB) in the guinea-pig is mediated by both tachykinin release from airway sensory nerve C-type fiber terminals and secondary synthesis of cysteinyl-leukotrienes, in particular LTD(4). Beta (beta)(2)-agonists are potent bronchodilators but potentially could also inhibit the airway response to hyperpnea challenge via effects on the release of LTD(4)from airway cells in vivo. The purpose of this study was to test the hypothesis that beta(2)agonists attenuate HIB in guinea-pigs, in part, by reduction in LTD(4)release in vivo. Twenty-six guinea-pigs (400-550 g) were anesthetized with xylazine (7 mg/kg) and pentobarbital (65 mg/kg), tracheotomized and mechanically ventilated with a small animal ventilator using a tidal volume of 3 ml and a breathing frequency of 60 breaths/min. Dry gas (95%O(2)/5%CO(2)) with a 4 ml tidal volume and a breathing frequency of 150/min was used for hyperpnea challenge. Challenge with isocapnic dry gas triggered a significant increase in pulmonary resistance (0.3 +/- 0.02 vs. 0.57 +/- 0.06 cmH(2)O/ml per s; P=0. 017; n=13) and excretion of LTD(4)in the bile (baseline: 2.43 vs. HIB: 4.66 pmol/h; P=0.04). Salbutamol pretreatment completely blocked the airway response to the challenge (0.3+/-0.02 vs. 0.3+/-0. 05 cmH(2)O/ml per s; n=13) and reduced the biliary excretion of LTD(4)(baseline: 2.42 pmol/h; vs. HIB: 2.40 pmol/h). We conclude that salbutamol inhibited the airway responses to dry gas hyperpnea challenge and LTD(4)synthesis by the airway cells.

Adrenergic beta-2 Receptor Agonists↗
PubMed1994

Ipratropium bromide protects against bronchoconstriction during bronchoscopy.

Pulmonary function is reportedly impaired by fiberoptic bronchoscopy. We investigated the effect of two anticholinergic agents, intramuscular atropine and inhaled ipratropium bromide, on bronchoconstriction in 29 patients who were undergoing diagnostic bronchoscopy. The patients were divided into three groups; the first received 0.5 mg of atropine intramuscularly; the second took four puffs of 0.02 mg ipratropium bromide aerosolized by a metered-dose inhaler, and the third inhaled four puffs of a placebo. Fifteen minutes later a standardized topical anesthetic, lidocaine, was administered, and a bronchoscopic examination was performed. Pulmonary function was measured before and 15 minutes after each step. Pulmonary function was not affected by the treatment with anticholinergics or the placebo. In the placebo and the atropine groups, the topical anesthesia produced significant reductions in forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate (PEFR); further reductions in these values were observed after bronchoscopy. In the group treated with ipratropium bromide there were no significant changes in FEV1 and PEFR after topical anesthesia. Bronchoscopy induced significant reductions in FEV1 and PEFR, but the changes were significantly smaller than those seen in the placebo and atropine groups. The results suggest that the deleterious effect of bronchoscopy on pulmonary function is due to topical lidocaine anesthesia and to the bronchoscopic examination itself. Inhaled ipratropium bromide protects against these deleterious effects, whereas intramuscular atropine does not.

Administration, Inhalation↗
PubMed1992

CP-96,345, a non-peptide antagonist of substance P: II. Actions on substance P-induced hypotension and bronchoconstriction, and on depressor reflexes in mammals.

In order to extend the in vivo pharmacological profile of CP-96,345 ((2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)- methyl)-1-azabicyclo[2.2.2]octan-3-amine dihydrochloride), a non-peptide antagonist of substance P, the compound was tested against substance P-induced effects on blood pressure in rabbits and on respiration pressure in guinea-pigs. In addition, CP-96,345, and its inactive (2R,3R)-enantiomer, CP-96,344, were also tested in 2 models involving presumably substance P-mediated reflexes in the rat. The fall in blood pressure evoked by i.v. injections of substance P in the rabbit was inhibited by 0.3 mumol kg-1 CP-96,345 i.v. for at least 30 min, and almost abolished, for at least 2 h, by 3 mumol kg-1. In guinea-pigs, the bronchoconstriction induced by i.v. injections of substance P, but not that in response to histamine or bradykinin, was inhibited by CP-96,345 (0.6 and 6.0 mumol kg-1, i.v.) in a dose-dependent manner and this inhibition lasted for 40 min and 70 min, respectively. CP-96,345 (3-20 mumol kg-1, i.v.) reduced depressor reflexes in response to stimulation of peripheral capsaicin-sensitive neurones in the rat. However, the inhibition was not dose-dependent and was also seen with the inactive enantiomer, CP-96,344. This effect can hardly be attributed to receptor-specific effects of CP-96,345 and may be related to unspecific actions such as those involved in the cardiac depression exhibited by both enantiomers. The present results show that CP-96,345 is a potent antagonist of substance P in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Salmeterol protects against hyperventilation-induced bronchoconstriction over 12 hours.

To study the dose-response relationship of salmeterol for protection against a naturally occurring stimulus, isocapnic hyperventilation tests of cold air were done in 16 asthmatic patients. The subjects inhaled either 50 micrograms salmeterol, salbutamol 200 micrograms, or placebo in a double-blind, randomised, cross-over study. The FEV1 was measured prior to medication and the provocative ventilation (PV20) required to induce a 20% fall in FEV1 was calculated by linear interpolation from ventilation-response curves obtained 0.5, 4, 8, and 12 h after medication. Following salbutamol, the mean FEV1 were 4.11, 3.89, 3.58, and 3.55 l, with a significant difference from placebo up to 4 h. Following salmeterol, mean FEV1 values were 3.95, 4.10, 3.93, and 3.88 l, with a significant difference from placebo up to 12 h. The mean PV20FEV1 after salbutamol was 78.8, 58.5, 52.7, and 48.4 l.min-1, the 0.5 h value being significantly different from placebo. After salmeterol, the mean PV20FEV1 values were 84.6, 82.5, 67.8, and 65.8 l.min-1, with a significant difference from placebo up to 12 h. We conclude that, besides its long-lasting bronchodilating effect, salmeterol protects against hyperventilation-induced bronchoconstriction for at least 12 h.

Adult↗
PubMed1994

Effect of BAY x 7195, an oral receptor antagonist of cysteinyl-leukotrienes, on leukotriene D4-induced bronchoconstriction in normal volunteers.

Leukotrienes (LT) have been proposed to play an important role in the pathogenesis of asthma. This paper reports the results of two studies investigating the effect of BAY x 7195, a new oral receptor antagonist of cysteinyl-leukotrienes, on LTD4-induced bronchoconstriction in healthy male volunteers. Using a double-blind, placebo-controlled, crossover design, volunteers received 250 mg (n = 6; study 1) and 100 and 500 mg (n = 6; study 2) of BAY x 7195. Bronchoprovocation with nebulized LTD4 was performed 2 (250 mg) and 2 and 8 (100 and 500 mg) h p.a. The specific airway's conductance (SGaw) was used to assess the airway's response. Blood samples to determine plasma concentrations of BAY x 7195 were taken at the end of bronchoprovocation. BAY x 7195 showed no effect on baseline lung function. Compared to placebo, the different doses of BAY x 7195 increased the concentration of LTD4 needed to produce a 35% decrease in SGaw 2 h p.a. between 1- and 23-fold. Eight hours p.a., 100 and 500 mg caused shifts in the concentration-response curve of between 1- and 13-fold. There was no predictive relationship between plasma concentrations of BAY x 7195 and the response to LTD4 challenge. However, there was a relationship between dose and effect. No relevant adverse effects were reported. In conclusion, the present results suggest that BAY x 7195 is an effective LTD4-receptor antagonist in man.

Administration, Inhalation↗
PubMed1997

Midazolam reverses histamine-induced bronchoconstriction in dogs.

PURPOSE: Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the airway. METHODS: After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized with 30 mg.kg-1 pentobarbitone iv, and were paralysed with 200 micrograms.kg-1.hr-1 pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH image program. Bronchoconstriction was produced with histamine (H) 10 micrograms.kg-1 followed by 500 micrograms.kg-1.hr-1. Thirty minutes later, 0 [saline], 0.01, 0.1 and 1.0 mg.kg-1 midazolam and 25 micrograms.kg-1 flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured five minutes after each midazolam and flumazenil iv. At the same time, arterial blood was sampled for plasma catecholamine measurement. RESULTS: Histamine infusion decreased BCA to 49.7 +/- 17.3% of basal BCA. More than 0.1 mg.kg-1 midazolam increased BCA up to 71.7 +/- 15.3% of the basal (1.0 mg.kg-1) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 +/- 3.8 to 3.7 +/- 1.9 ng.ml-1 by 1.0 mg.kg-1 midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. CONCLUSION: Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil.

Anesthetics, Intravenous↗
PubMed1994

A comparison of sevoflurane with halothane, enflurane, and isoflurane on bronchoconstriction caused by histamine.

This study was conducted to assess the effect of sevoflurane on lung resistance and compliance, and its responsiveness to histamine. We studied eight dogs to compare the effect of sevoflurane, isoflurane, enflurane, and halothane on bronchoconstriction caused by histamine. Baseline values of pulmonary resistance (RL) and dynamic pulmonary compliance (Cdyn) were measured prior to administration of histamine. Histamine (2, 4, and 8 micrograms.kg-1) were administered iv, and the values of RL and Cdyn at the time of peak effect were recorded. Under 1 or 2 MAC anaesthesia, sevoflurane as well as the other three anaesthetics had no bronchoactive effects. The four anaesthetics, including sevoflurane, demonstrated inhibitory effect on increases in RL and decreases in Cdyn caused by histamine. At 1 MAC anaesthesia, % changes in RL caused by 2, 4, or 8 micrograms.kg-1 of histamine were 38 +/- 11, 85 +/- 21, or 132 +/- 24% (mean +/- SE) for halothane, and 65 +/- 11, 132 +/- 15, or 172 +/- 19% for sevoflurane, respectively. Sevoflurane was less effective than halothane in preventing increases in RL. In preventing decreases in Cdyn, sevoflurane was less effective than halothane only at 8 micrograms.kg-1 of histamine under 1 and 2 MAC anaesthesia. There was no difference in attenuating effect on changes in RL and Cdyn between sevoflurane and isoflurane or enflurane. We concluded that sevoflurane was less potent than halothane in attenuating changes in RL and Cdyn in response to iv histamine.

Airway Resistance↗
PubMed2003

Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice.

OBJECTIVE AND DESIGN: Asthma is an inflammatory disease of the airways and the current focus in managing asthma is the control of inflammation. In this study, we attempted to investigate the anti-asthmatic potential of a plant derived natural compound, luteolin. MATERIAL: We used a murine model of airway hyperreactivity, which mimicked some of the characteristic features of asthma. Male BALB/c mice (8-9 weeks) were used for this study. TREATMENT: Mice (n = 6) were sensitized by intraperitoneal (i. p.) injection of 10 mg of ovalbumin (OVA) on days 0, 7 and 14 followed by aerosol inhalation (5% OVA) treatments daily beginning from day 19 to day 23. To study its preventive effect, luteolin (0.1, 1.0, and 10 mg/kg body weight; daily) was administered orally during the entire period (0 to 23 day) of sensitization. To study its curative effect, mice were first sensitized and then luteolin (1.0 mg/kg body weight daily) was given orally from day 26 to 32. The airway hyperreactivity, immunoglobulin E (IgE) in the sera, and cytokines (IFN-gamma, IL-4 and IL-5) in the bronchoalveolar lavage fluid (BALF) were measured. RESULTS: Both during sensitization and after sensitization, luteolin, at a dose of 0.1 mg/kg body weight, significantly modulated OVA-induced airway bronchoconstriction and bronchial hyperreactivity (p < 0.05). Luteolin also reduced OVA-specific IgE levels in the sera, increased interferon gamma (IFN-gamma) levels and decreased the interleukin-4 (IL-4) and interleukin-5 (IL-5) levels in the BALF. CONCLUSION: Our study showed that luteolin treatment during and after sensitization significantly attenuated the asthmatic features in experimental mice. Therefore, luteolin could be used either as a lead molecule to identify an effective antiasthma therapy or as a means to identify novel anti-asthma targets.

Airway Resistance↗
PubMed1999

Mediators in hyperpnea-induced bronchoconstriction of guinea pigs.

Both tachykinins and leukotrienes (LTs) have been demonstrated to be the mediators for hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. We tested the hypothesis that leukotrienes modulate HIB indirectly by triggering tachykinin release. Ninety nine young guinea pigs were divided into four groups: control; LTC4; FPL 55712 (a LT receptor antagonist); and MK-886 (an inhibitor of LT synthesis). Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. The protocol included the baseline, hyperpnea, and recovery periods. Thus, animals in each group were further divided into three subgroups: baseline; recovery-3 min; and recovery-8 min. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 s (FEV0.1) and maximal expiratory flow at 30% total lung capacity (Vmax30), as well as determined substance P (SP) and LT levels in plasma and bronchoalveolar lavage (BAL) during either the baseline or the recovery (3 or 8 min) period. Hyperpnea caused decreases in Crs, FEV0.1 and Vmax30, indicating HIB, in the control group at 3 min and 8 min of the recovery period. Both FPL 55712 and MK-886 significantly attenuated HIB. In the control group, hyperpnea caused significant increases in SP and LT levels in both plasma and BAL. These increases in SP levels were significantly suppressed, however, by FPL 55712 and MK-886. Compared to the control group, infusion of LTC4 did not significantly alter either HIB, SP or LT levels in most cases. An additional group of 24 animals treated with neurokinin-2 receptor antagonist, SR 48968, demonstrated that SR 48968 significantly suppressed hyperpnea-induced increases in plasma, but not in BAL, LT levels. Since FPL 55712 and MK-886 first suppress LT activities, these results suggest that suppressed LT activities attenuate HIB indirectly via reducing tachykinin release.

Animals↗
PubMed2005

Exercise-induced bronchoconstriction: pathogenesis.

There is still active debate on the acute mechanism of exercise-induced bronchoconstriction (EIB). Although it is unlikely that vasoconstriction and hyperemia of the bronchial vasculature are essential events for EIB, it is likely that this vasculature enhances the airway response to dehydration and contributes to the pathogenesis of EIB, particularly in elite athletes. Accumulating evidence suggests that airway smooth muscle (ASM) becomes more sensitive as a result of repeated exposure to bulk plasma in response to airway injury from dehydration. Recent evidence also demonstrates sufficient concentrations of mediators that could affect ASM. Paradoxically, mediator release from mast cells may be enhanced and their contractile effects greater when beta(2)-receptor agonists are taken daily. The effect of drugs that have the potential to reduce microvascular leak and reduce or inhibit release or action of these mediators needs to be investigated in elite athletes.

Adrenergic beta-2 Receptor Agonists↗
PubMed1991

Hypothermia augments non-cholinergic neuronal bronchoconstriction in pithed guinea-pigs.

Electrical stimulation at C4-C7 in the spinal canal of pithed guinea-pigs injected with atropine, d-tubocurarine and pentolinium caused frequency-dependent bronchoconstriction. Such non-cholinergic responses to electrical stimulation, unlike responses to substance P, were abolished by pretreatment with capsaicin but not by mepyramine or propranolol. Bronchoconstrictor responses to electrical stimulation were inversely related to rectal temperature (between 30-40 degrees C) whereas responses to substance P increased with increasing temperature over the same range. Ouabain (i.v.) augmented responses to electrical stimulation at 35-37 degrees C but depressed those at 30-32 degrees C. Both morphine and the alpha 2-adrenoceptor agonist B-HT920 (i.v.) inhibited non-cholinergic-mediated bronchoconstrictor responses at 30-32 degrees C. These results stress the importance of adequate control of body temperature in this preparation. Lowered body temperature may increase neuronal output of neuropeptides whilst depressing bronchial smooth muscle sensitivity. The data support previous conclusions regarding the role of Na+/K+ activated ATPase in temperature-induced changes in sensitivity to bronchoconstrictor stimuli.

Adrenergic alpha-Agonists↗
PubMed1993

The inhibitory effects of Ro 31-6930 and BRL 38227 on cholinergically-mediated bronchoconstriction in the guinea-pig.

This study compares the effects of two K(+0-channel openers, Ro 31-6930 and BRL 38227, on cholinergically-evoked contraction of guinea-pig airways to examine whether either compound acts through prejunctional inhibition of the release of acetylcholine. In the isolated trachea, Ro 31-6930 and BRL 38227 evoked concentration-dependent inhibition of tone generated by electrical field stimulation with pD2 values of 7.03 (6.77-7.29) and 6.26 (5.91-6.61) respectively and of that elicited by acetylcholine with pD2 values of 7.38 (6.52-8.24) and 6.65 (6.16-7.13). Neither compound was more potent against responses to electrical field stimulation than against acetylcholine. In the anaesthetised guinea-pig, Ro 31-6930 inhibited the bronchoconstriction evoked by bilateral vagus nerve stimulation and intravenous acetylcholine with ID50 values of 12.9 +/- 3.9 and 3.6 +/- 1.3 micrograms/kg i.v. respectively. The corresponding values for BRL 38227 were 356 +/- 157 and 37.9 +/- 13.4 micrograms/kg i.v. respectively. Thus, in vivo, both compounds were more potent against acetylcholine than against vagal stimulation. These results provide indirect evidence that K(+)-channel openers do not inhibit the release of acetylcholine from parasympathetic nerves in guinea-pig airway smooth muscle.

Acetylcholine↗
PubMed1993

Endogenous nitric oxide counteracts antigen-induced bronchoconstriction.

In anesthetized, artificially ventilated guinea pigs immunized against ovalbumin, challenge with aerosolized ovalbumin (0.1 mg) elicited a substantial and sustained increase of insufflation pressure. The inhibitor of endogenous nitric oxide (NO) synthesis, L-NAME (N omega-nitro-L-arginine methylester, 30 mg kg-1 i.v.), markedly augmented the response, the potentiation of which could be prevented by NO (20 p.p.m.) in the inhaled air. The results indicate an inhibitory effect of endogenous NO on antigen-induced bronchoconstriction.

Aerosols↗