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PubMed2003

Effects of propofol on bronchoconstriction and bradycardia induced by vagal nerve stimulation.

BACKGROUND: Vagolysis has been considered as a mechanism by which propofol produces bronchodilation. However, it has also been suggested that propofol-induced bradycardia may result from increased vagal tone. In this study, we have determined whether propofol has vagolytic effects on both the airway and cardiovascular system. METHODS: Mongrel dogs were anesthetized with pentobarbital. Bronchoconstriction was assessed by measuring changes in a bronchial cross-sectional area (BCA) using a bronchoscopic method. Heart rate (HR) and direct arterial blood pressure were also monitored. Vagal nerve stimulation (VNS) was performed for 60 s to produce both bronchoconstriction and bradycardia. To determine the effect of propofol on VNS-induced bronchoconstriction and bradycardia (n = 7), 0 (saline), 2.0 and 20 mg/kg propofol were administered intravenously at 20-min intervals with VNS commenced 5 min later. In addition, to determine if propofol-induced bradycardia is due to a vagomimetic action, two groups of six dogs were given 20 mg/kg propofol with or without 0.2 mg/kg atropine pre-treatment. HR was measured before and 5 min after propofol. RESULTS: Propofol 20 mg/kg significantly inhibited VNS-induced bronchoconstriction. Although propofol per se significantly reduced HR (24%) and blood pressure (37%), the reduction in HR produced by VNS after 20 mg/kg propofol did not differ from that after saline or the lower dose of propofol (2 mg/kg). As atropine pre-treatment did not attenuate propofol-induced bradycardia, this response is unlikely to be simply due to vagomimetic actions. CONCLUSION: Propofol has vagolytic effects on the airway but does not worsen bradycardia produced by parasympathetic stimulation.

Anesthetics, Intravenous↗

PubMed1999

Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5'-monophosphate-induced bronchoconstriction in patients with COPD.

BACKGROUND: Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP. OBJECTIVE: To investigate the mechanism of AMP-induced bronchoconstriction in COPD. METHODS: We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60+/-7 years, FEV1 61+/-12% of predicted and FEV1/VC 51+/-8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 microg of inhaled ipratropium bromide, or placebo. RESULTS: GM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P<0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P<0.0001). CONCLUSION: These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.

Adenosine Monophosphate↗

PubMed2000

Influence of alpha-adrenoceptor blockade on antigen- and propranolol-induced bronchoconstriction in guinea-pigs in vivo.

1. Beta-adrenoceptor antagonists, such as propranolol, can provoke severe bronchoconstriction only in asthmatic subjects. Recently, we developed a guinea-pig model of propranolol-induced bronchoconstriction (PIB) and the purpose of this study was to investigate the role of alpha-adrenergic nerve pathways in this reaction. 2. Phentolamine administered after an antigen challenge did not inhibit PIB; however, its administration before the antigen challenge significantly inhibited the antigen-induced bronchoconstriction and also bronchoconstriction induced by methacholine inhalation. 3. We conclude that the alpha-adrenergic nerve system is not involved in the development of PIB following allergic reaction in our guinea-pig model.

Administration, Inhalation↗

PubMed2003

Perception of dyspnea during exercise-induced bronchoconstriction.

UNLABELLED: After strenuous physical exercise, many subjects show a significant bronchoconstriction and report dyspnea. Despite this clinical condition being a commonly encountered situation during daily life, which may be responsible for substantial disability there is little information on the relationship between the perception of dyspnea and exercise-induced bronchoconstriction (EIB) after a standardized exercise challenge. For these reasons, we evaluated 200 consecutive outpatients (median age 13 years, ranging from 5 to 56 years) referred to our laboratory to perform an exercise test out of suspicion of EIB. On exercise challenge, perception of dyspnea was rated on a modified bipolar Borg scale immediately before each FEV1 measurement. Sixty-nine (35%) subjects had a positive exercise challenge, defined as a decrease of at least 20% in FEV1 from baseline. Both the onset and the decay of dyspnea preceded those of bronchoconstriction. Overall, the rating of dyspnea in the laboratory was well related with the reports of exercise-related symptoms. Similarly, 36 of 77 (47%) asthmatics with a history of exertional symptoms and 24 of 65 patients (40%) without a history had a positive challenge. Asthmatics reporting exertional symptoms perceived a greater magnitude of dyspnea after exercise independently from the degree of bronchoconstriction. Overall, dyspnea was significantly but loosely correlated to the magnitude of decrease in FEV1, being also influenced by age, gender and BMI. CONCLUSIONS: We conclude that dyspnea recorded in the laboratory after exercise test is related to exertional symptoms reported during real life, but not completely related to EIB. The rating of dyspnea is a well-suited model to study naturally occurring exercise-induced dyspnea and a useful tool to enlarge the results of an exercise challenge.

Adolescent↗

PubMed1998

Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction.

BACKGROUND: Patients with mild asthma frequently have only exercise-induced bronchoconstriction, a symptom of inadequate control of asthma. We evaluated the ability of montelukast, a leukotriene-receptor antagonist, to protect such patients against exercise-induced bronchoconstriction. METHODS: We randomly assigned 110 patients (age, 15 to 45 years) with mild asthma and a decrease in the forced expiratory volume in one second (FEV1) of at least 20 percent after exercise on two occasions during a placebo run-in period to receive 10 mg of montelukast (54 patients) or placebo (56 patients) once daily at bedtime for 12 weeks in a double-blind study. Treatment was followed by a two-week, single-blind washout period during which all patients received placebo. Exercise challenges were performed at base line; 20 to 24 hours after dosing at weeks 4, 8, and 12; and at the end of the washout period. The primary end point was the area under the curve for FEV1 (expressed as the percent change from base-line values) in the first 60 minutes after exercise. This measure summarized the extent and duration of bronchoconstriction after exercise. RESULTS: At 12 weeks, montelukast therapy offered significantly greater protection against exercise-induced bronchoconstriction than placebo therapy (expressed as the percentage of inhibition of the end points), as evidenced by the improvement in the area under the FEV1 curve (degree of inhibition, 47.4 percent; P=0.002). Montelukast therapy was also associated with a significant improvement in the maximal decrease in FEV1 after exercise (P=0.003) and the time from the maximal decrease in FEV1 to the return of lung function to within 5 percent of pre-exercise values (P=0.04). The differences between groups in the various measures of lung function were similar at 4, 8, and 12 weeks; there was no evidence of rebound worsening of lung function in the montelukast group after the washout period. After 12 weeks of treatment, patients in the montelukast group were more likely to rate their asthma control as better and less likely to require rescue therapy with a beta-agonist during or after exercise challenge. The rates of adverse events were similar in the two groups. CONCLUSIONS: As compared with placebo, once-daily treatment with montelukast provided significant protection against exercise-induced asthma over a 12-week period. Tolerance to the medication and rebound worsening of lung function after discontinuation of treatment were not seen.

Acetates↗

PubMed2003

Inhibitory effect of a leukotriene receptor antagonist (montelukast) on neurokinin A-induced bronchoconstriction.

BACKGROUND: Tachykinins are potent contractors of human airways producing a dose-related bronchoconstriction when administered by means of inhalation to asthmatic subjects. OBJECTIVE: The aim of this study was to examine the effective role played by leukotrienes (LTs) in neurokinin A (NKA)-induced bronchoconstriction in asthmatic patients. METHODS: To address this question, we investigated the protective effect of a selective cysteinyl LT receptor antagonist, montelukast, against inhaled NKA and determined LTE(4) excretion in the urine. RESULTS: Inhaled NKA in the absence of any drug treatment produced a concentration-related bronchospasm with a geometric mean provocative concentration required to produce a 15% decrease in FEV(1) from the postsaline baseline value (PC(15)) value of 290.9 microg/mL (+SE, 407.1 microg/mL; -SE, 207.84 microg/mL). Montelukast pretreatment significantly increased (P <.01) the PC(15) NKA value (708.8 microg/mL; +SE, 890.47 microg/mL; -SE, 564.15 microg/mL) in comparison with placebo (394.4 microg/mL; +SE, 491.88 microg/mL; -SE, 248.16 microg/mL) and produced a shift of the NKA concentration-response curve to the right in all the subjects studied. When compared with placebo, montelukast did not have a significant protective effect against methacholine challenge; the geometric mean PC(15) values obtained were 0.87 and 0.96 mg/mL with placebo and montelukast, respectively. Although we have not observed any increase in urinary LTE(4) excretion after NKA inhalation, we have shown that pretreatment of asthmatic subjects with montelukast elicits a significant protection against NKA-induced bronchoconstriction. CONCLUSION: In asthmatic subjects NKA-induced bronchoconstriction is indirectly caused by the release of LTs, and this mechanism could explain some of the antiasthmatic and anti-inflammatory effects of LT antagonists.

Acetates↗

PubMedDate not supplied

Importance of the angiotensin type 1 receptor in angiotensin II-induced bronchoconstriction and bronchial hyperresponsiveness in the guinea pig.

Although angiotensin II (Ang II) causes bronchoconstriction and bronchial hyperresponsiveness to methacholine in mildly asthmatic patients, the responsible mechanisms for these reactions are unclear. The authors examined the effect of intravenous infusion of Ang II on airway constriction in guinea pigs. Furthermore, the effects of subthreshold concentrations of Ang II on bronchial responsiveness to methacholine were investigated. Airway opening pressure (Pao), an index of bronchoconstriction, increased dose dependently after intravenous infusion of 3 and 10 nmol/kg Ang II (72.2 and 236.5 increase above the baseline value, respectively). In another set of experiments, animals received a methacholine inhalation challenge under a constant intravenous infusion of a subthreshold dose of Ang II (2 nmol/kg/min). The Ang II infusion elicited bronchial hyperresponsiveness to methacholine. The provocative concentration of methacholine, which produced a 200% increase above the baseline Pao (PC200), decreased from 306.9 to 156.1 micrograms/mL upon Ang II infusion. Pretreatment with TCV-116, a type 1 Ang II (AT1) receptor antagonist, but not PD123319, a type 2 Ang II (AT2) receptor antagonist, dose dependently prevented both the Ang II-induced bronchoconstriction and bronchial hyperresponsiveness to methacholine. The authors conclude that Ang II caused bronchoconstriction and induced bronchial hyperresponsiveness to methacholine via the AT1 receptors and that this effect did not involve the release of other bronchoactive mediators.

Angiotensin II↗

PubMed1999

Difference in bronchoprotective effects of bronchodilators on postallergic propranolol-induced bronchoconstriction.

Administration of propranolol provokes bronchoconstriction only in asthmatic patients. It is unknown whether bronchodilator therapy can prevent the propranolol-induced bronchoconstriction (PIB). We previously reported an animal model of PIB in which bronchoconstriction is caused by propranolol when inhaled 20 minutes after an antigen provocation in passively sensitized guinea pigs. Our goal was to evaluate the bronchoprotective effects of bronchodilators on the PIB in our animal model. Propranolol was inhaled 20 minutes after an antigen challenge in passively sensitized, anesthetized, and artificially ventilated guinea pigs. Atropine (5 mg/kg) and equipotent doses of salbutamol (0.6 microgram/kg) and aminophylline (25 mg/kg), which were determined by the dose-response curves for inhibition of histamine-induced bronchoconstriction, were intravenously administered 5 minutes before the propranolol inhalation. Treatment of the animals with 25 mg/kg of aminophylline, but not with 0.6 microgram/kg of salbutamol or 5 mg/kg of atropine, significantly prevented the PIB. These results show that our animal model is an experimental model of PIB which is resistant to beta 2-agonists or anticholinergics and suggest that aminophylline may be useful to prevent and treat PIB resistant to beta 2-agonists.

Airway Resistance↗

PubMed2000

The inhibitory effect of anti-allergic agent suplatast tosilate (IPD-1151T) on methacholine- and allergen-induced bronchoconstriction in sensitized mice. asakazu@med.showa-u.dc.jp.

The influence of an anti-allergic agent, suplatast tosilate (IPD-1151T; (+/-)-[2-[4-(3-ethoxy-2-hydroxypropoxy)phenyl-carbamoyl]-ethyl] dimethylsulfonium p-toluenesulfonate) on allergic bronchoconstriction induced by allergen and methacholine (MCh) were examined in mice. BALB/c mice were sensitized by intraperitoneal injection of dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) mixed with A1(OH)3 (DNP-KLH). IPD-1151T was administered orally once a day for either 5 or 14 days in doses of 10, 30 or 100 mg/kg. Bronchoconstriction was measured 24h after the final drug administration. IPD-1151T inhibited both antigen- and MCh-mediated bronchoconstriction in actively sensitized mice. The inhibition induced was closely related to the dose and frequency of oral administration of the agent. We also examined the effect of IPD-1151T on IgE production in response to DNP-KLH immunization. IPD-1151T inhibited dose-dependently both total and specific IgE concentrations in serum prepared from mice 15 days after immunization. These results strongly indicate that IPD-1151T inhibits IgE production in vivo and results in attenuating effect on bronchoconstriction.

Allergens↗

PubMed2001

Comparison of relaxant effects of propofol on methacholine-induced bronchoconstriction in dogs with and without vagotomy.

Propofol has been suggested to have in vivo airway relaxant effects, although the mechanism is still unclear. In this study, we determined whether propofol could antagonize methacholine-induced bronchoconstriction and determined whether vagotomy modifies this relaxant effect. Fourteen mongrel dogs anaesthetized with pentobarbital and pancuronium were assigned to a control group (n=7) and a vagotomy group (n=7). The trachea was intubated with a special endotracheal tube that had a second lumen for insertion of the bronchoscope. Bronchial cross-sectional area, which was monitored continuously through the bronchoscope, was measured with image analysis software. Bronchoconstriction was elicited with methacholine (0.5 microg kg(-1) + 5.0 microg kg(-1) min(-1)) until the end of the experiment. Thirty minutes after the start of methacholine infusion, propofol 0, 0.2, 2.0 and 20 mg kg(-1) was administered. Changes in bronchial cross-sectional area were expressed as percentages of the basal area. Plasma concentrations of propofol and catecholamine were measured by high-performance liquid chromatography. Maximal inhibition (bronchoconstriction = 0%, baseline = 100%) and IC50 (concentration producing 50% inhibition of maximal effect) produced by propofol was obtained from each concentration-response curve using a curve-fitting program. Methacholine decreased bronchial cross-sectional area to 49.3% (95% confidence interval 38.5-60.1%) and 45.3% (34.8-55.7%) of the baseline value. Propofol 20 mg kg(-1) significantly reversed this effect: bronchial cross-sectional area was reduced to 77.8% (66.2-89.6%) and 75.9% (64.0-87.9) in the control and vagotomy groups respectively. The two groups did not differ significantly in the maximal inhibitory effect of propofol [control group, 61.1% (46.3-75.9%), vagotomy group, 64.2% (40.1-88.3%)] or pIC50 [control group 5.03 (4.55-5.51), vagotomy group 4.86 (4.49-5.24)]. Therefore, the relaxant effects of propofol on methacholine-induced bronchoconstriction may not be mediated centrally. Propofol may relax airway smooth muscles directly or through the peripheral vagal pathway.

Anesthetics, Intravenous↗

PubMed2000

A comparison of the spasmolytic effects of olprinone and aminophylline on serotonin-induced pulmonary hypertension and bronchoconstriction with or without beta-blockade in dogs.

In the present study in dogs, we compared with aminophylline the spasmolytic effects of olprinone, a novel phosphodiesterase 3 inhibitor, on serotonin-induced pulmonary hypertension (PH) and bronchoconstriction. Mongrel dogs were anesthetized with pentobarbital. PH and bronchoconstriction were induced with serotonin: 10 microg/kg + 1 mg x kg(-1) x h(-1), and assessed as % changes in pulmonary vascular resistance and bronchial cross-sectional area (basal = 100%). Initially, the relaxant effects of olprinone (n = 8: 0-1000 microg/kg) and aminophylline (n = 8: 0-100 mg/kg) were compared. Pulmonary vascular resistance and bronchial cross-sectional area were assessed before and 30 min after serotonin infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 microg/kg, n = 6) or aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each). Olprinone and aminophylline dose-dependently attenuated both PH and bronchoconstriction (olprinone > aminophylline: -logED(50)[mean] for PH and bronchoconstriction 5.37+/- 0.35[4.24 microg/kg] vs. 1.60+/-0.23[25.4 mg/kg] and 4.06+/-0.12[87.8 microg/kg] vs. 1.51+/-0.21[30.6 mg/kg], respectively). In addition, olprinone produced more potent pulmonary vasodilation than bronchodilation while aminophylline was equipotent. In addition, there was a significant increase in plasma catecholamines after olprinone (> or =100 microg/kg) and aminophylline (> or =10 mg/kg). With the exception of aminophylline-induced bronchodilation, propranolol did not reverse any of the other effects measured. Therefore, the spasmolytic effects of olprinone are independent of plasma catecholamines, while the bronchodilating effect of aminophylline may partially involve increased levels of circulating catecholamines.

Adrenergic beta-Antagonists↗

PubMed1998

Platelet-activating factor is a key mediator of pulmonary vasoconstriction and bronchoconstriction after antigen challenge in the perfused sensitized rabbit lung.

Exposure of sensitized perfused rabbit lungs to human O-N type erythrocytes leads to pulmonary vasoconstriction and bronchoconstriction. To investigate whether platelet-activating factor (PAF) is a mediator of pulmonary vasoconstrictive and bronchoconstrictive responses after antigen challenge, we administered antigenic erythrocytes after the administration of PAF antagonist (.1 mg/kg; CV6209). Pulmonary arterial and airway pressures significantly increased after antigen challenge in the sensitized rabbit lungs, but not in the nonsensitized rabbit lungs. CV6209 significantly inhibited these pulmonary vasoconstrictive and bronchoconstrictive responses after antigen challenge. We concluded that PAF, at least in part, plays an important role in pulmonary vasoconstriction and bronchoconstriction after antigen challenge in rabbits.

Animals↗

PubMed2005

Return to play following exercise-induced bronchoconstriction.

OBJECTIVE: To review evidence-based support for return to play criteria following acute exercise-induced bronchoconstriction. DATA SOURCES: Electronic databases Ovid Medline and PubMed were searched for papers relating to exercise related asthma and bronchoconstriction and return to play criteria. Additional references from the bibliographies of retrieved articles were also reviewed. DATA SYNTHESIS: There is clear evidence that exercise-induced airways narrowing is increasing in prevalence among athletes from school children to Olympians to professionals, yet there have been no studies specifically addressing return to play criteria. Although deaths from exercise associated bronchoconstriction were previously thought to be rare, recent reports of such deaths call for increased awareness by physicians, athletic trainers, and coaches of the potential fatal consequences of unrecognized episodes or of inadequate treatment. CONCLUSIONS: No agreed-upon protocol for safe return to play following an acute episode of exercise induced bronchoconstriction has been published. A specific detailed protocol for return to play would assist physicians and other heath professionals to determine with greater confidence that an athlete is fully recovered and can safely return to play.

Asthma, Exercise-Induced↗

PubMed1994

Aerosolized acetaldehyde, but not ethanol, induces histamine-mediated bronchoconstriction in guinea-pigs.

It was reported that ethanol-induced bronchoconstriction was associated with elevated serum levels of acetaldehyde and histamine in Japanese asthmatic patients, but there is no study to investigate the airway response to acetaldehyde. We performed this animal study to test the hypothesis that acetaldehyde has the bronchospastic action via histamine release. First, we investigated the airway response to ascending doses (31.3, 62.5, 125, and 250 mM) of inhaled ethanol or acetaldehyde in guinea-pigs. Secondly, guinea-pigs pretreated with intraperitoneal injection of saline or 20 mg/kg diphenhydramine inhaled acetaldehyde. Finally, guinea-pigs pretreated with intraperitoneal injection of saline or 0.5 mg/kg atropine sulfate inhaled acetaldehyde. Inhalation of acetaldehyde, but not ethanol, caused bronchoconstriction in a dose-dependent manner. The bronchoconstriction induced by inhaled acetaldehyde was completely prevented by pretreatment with diphenhydramine. Atropine had no preventing effect against the acetaldehyde-induced bronchoconstriction. In conclusion, acetaldehyde has the bronchospastic action via histamine release in guinea-pigs. It is suggested that histamine H1-antagonists may be available for preventing alcohol-induced asthma.

Acetaldehyde↗

PubMed1999

Different ion channel control pH6-induced bronchoconstriction and calcitonin gene-related peptide release in the guinea-pig lung.

We have studied the bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by perfusion of pH6 buffer in the isolated guinea-pig perfused lung. Both bronchoconstriction and peptide release were completely abolished after systemic capsaicin pretreatment. Ca(2+)-free pH6 buffer infusion also completely inhibited the bronchial response, whereas the calcitonin gene-related peptide-like immunoreactivity overflow was significantly reduced. omega-Conotoxine and omega-agatoxin IVA known as N-, L- and P-type Ca2+ channel blocker, respectively, and the Na+ channel blocker tetrodotoxin decreased significantly the pH6-induced bronchial response and calcitonin gene-related peptide like immunoreactivity overflow. Nifedipine was without influence suggesting the involvement of both P- and N-type Ca2+ channel as well as the activation of an axon reflex. Ruthenium red had a more pronounced reduction effect on the functional response than on the peptide release. Ryanodine and caffeine are both agents known to influence Ca2+ release from sarcoplasmic reticulum. Ryanodine significantly reduced both bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Caffeine as well as theophylline and the Na(+)-H+ blocker, dimethylamiloride, largely depressed the functional response while producing a significant increase of calcitonin gene-related peptide-like immuno-reactivity basal value. The pH6-induced peptide overflow was slightly inhibited after caffeine and dimethylamiloride pre-treatment whereas no significant change was observed after theophylline. It is concluded that multiple ion channels including different type of Ca2+ channels appear to participate in pH6-induced bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity release in the guinea-pig lung.

Animals↗

PubMed1998

Prejunctional control of pH 6-induced bronchoconstriction by NK1, NK2, mu-opioid, alpha2-adrenoceptor and glucocorticoid receptors in guinea-pig isolated perfused lung.

This study investigated the release of calcitonin-gene related peptide-like (CGRP) immunoreactivity and bronchoconstriction induced by pH 6 buffer in guinea-pig isolated perfused lung. Both pH 6-induced CGRP-like immunoreactivity and bronchoconstriction were completely abolished after systemic pretreatment with capsaicin. Pretreatment with the NK2 receptor antagonist SR 48968 (5 x 10(-7)M) completely inhibited bronchoconstriction and significantly reduced the immunoreactivity induced by the pH 6 buffer. The NK1 antagonist SR 140333 (5 x 10(-7)M) and, to a lesser extent the NK1 antagonist CP 96345, morphine (5 x 10(-6)M), the alpha2-adrenoceptor agonist UK 14304 (10(-7)M) and betamethasone (10(-6)M) significantly reduced both pH 6-induced bronchial response and CGRP-like immunoreactivity overflow. The effects of morphine and UK14304 were partially reversed by naloxone (5 x 10(-5)M) and idazoxan (5 x 10(-50M). Therefore, NK1, NK2, mu-opioid, alpha2-adrenoceptor and glucocorticoid receptors seemed to have a prejunctional action on pH 6 buffer-induced CGRP-like immunoreactivity and bronchoconstriction.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2002

Role of cysteinyl leukotrienes in adenosine 5'-monophosphate induced bronchoconstriction in asthma.

BACKGROUND: Adenosine induced bronchoconstriction in patients with asthma is thought to be mediated by the synthesis and release of autacoids from airway mast cells. In vitro, adenosine induced constriction of asthmatic bronchi is blocked by a combination of specific histamine and cysteinyl leukotriene receptor antagonists, but the relative contribution of these mediators in vivo is unclear. We hypothesised that adenosine induced bronchoconstriction in asthmatic patients may be blocked by pretreatment with the orally active selective cysteinyl leukotriene-1 (CysLT(1)) receptor antagonist, montelukast. METHODS: In a randomised, double blind, crossover study, oral montelukast (10 mg) or placebo was administered once daily on two consecutive days to 18 patients with mild to moderate persistent atopic asthma. Incremental doses of adenosine 5'-monophosphate (AMP) from 0.39 to 400 mg/ml were inhaled by dosimeter and the dose producing a 20% fall in FEV(1) (PC(20)AMP) after AMP inhalation was recorded. Leukotriene E(4) (LTE(4)) urinary concentrations were measured by enzyme immunoassay 4 hours after AMP challenge. RESULTS: Montelukast pretreatment provided highly significant protection against adenosine induced bronchoconstriction, with geometric mean PC(20)AMP values of 52.6 mg/ml (95% CI 35.2 to 78.7) after placebo and 123.9 mg/ml (95% CI 83.0 to 185.0) after montelukast (p=0.006). The geometric mean of the montelukast/placebo PC(20)AMP ratio was 2.4 (95% CI 1.3 to 4.2). Montelukast had no significant effect on 4 hour urinary excretion of LTE(4) compared with placebo. CONCLUSIONS: Selective CysLT(1) receptor antagonism with montelukast provides highly significant protection against AMP induced bronchoconstriction in patients with atopic asthma, implying that cysteinyl leukotrienes are generated from airway mast cells through preferential activation of their A(2B) receptors.

Acetates↗

PubMed1997

Attenuation of propranolol-induced bronchoconstriction by frusemide.

BACKGROUND: Inhaled propranolol causes bronchoconstriction in asthmatic subjects by an indirect mechanism which remains unclear. Inhaled frusemide has been shown to attenuate a number of indirectly acting bronchoconstrictor challenges. The aim of this study was to investigate whether frusemide could protect against propranolol-induced bronchoconstriction in patients with stable mild asthma. METHODS: Twelve asthmatic subjects were studied on three separate days. At the first visit subjects inhaled increasing doubling concentrations of propranolol (0.25-32 mg/ml), breathing tidally from a jet nebuliser. The provocative concentration of propranolol causing a 20% reduction in FEV1 (PC20FEV1 propranolol) was determined from the log concentration-response curve for each subject. At the following visits nebulised frusemide (4 ml x 10 mg/ml) or placebo (isotonic saline) was administered in a randomised, double blind, crossover fashion. FEV1 was measured immediately before and five minutes after drug administration. Individual PC20FEV1 propranolol was then administered and FEV1 was recorded at five minute intervals for 15 minutes. Residual bronchoconstriction was reversed with nebulised salbutamol. RESULTS: Frusemide had no acute bronchodilator effect but significantly reduced the maximum fall in FEV1 due to propranolol: mean fall 18.2% after placebo and 11.8% after frusemide. The median difference in maximum % fall in FEV1 within individuals between study days was 3.6% (95% CI 1.2 to 11.7). CONCLUSIONS: Frusemide attenuates propranolol-induced bronchoconstriction, a property shared with sodium cromoglycate. Both drugs block other indirect challenges and the present study lends further support to the suggestion that frusemide and cromoglycate share a similar mechanism of action in the airways.

Adrenergic beta-Antagonists↗