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Results for “Bronchoconstriction”

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At least 127 records · Page 7Linked to original sources

PubMed2001

Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction.

To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg(-1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg(-1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated.

Animals↗

PubMed2000

No involvement of lipid mediators in a guinea pig model of ultrasonically nebulized distilled water-induced bronchoconstriction.

An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We have reported that bronchoconstriction occurs immediately after UNDW is inhaled 20 min after an antigen challenge in guinea pigs. Our aim was to examine the role of lipid mediators in this response. Passively sensitized guinea pigs were anesthetized and artificially ventilated. A sulfidopeptide leukotriene receptor antagonist, KCA-757, and platelet-activating factor antagonists, Y-24180 and E6123, were administered i.v. 15 min after an aerosolized antigen challenge, and UNDW was inhaled 5 min later. KCA-757, Y-24180, or E6123 did not, significantly alter the UNDW-induced bronchoconstriction. Together with our previous data that thromboxane A2 receptor antagonists did not influence the UNDW-induced bronchoconstriction, the present results suggest that lipid mediators are not involved in the UNDW-induced bronchoconstriction in our guinea pig model.

Animals↗

PubMed2006

Perception of dyspnea during exacerbation and histamine-related bronchoconstriction in patients with asthma.

BACKGROUND: Numerous studies have been performed concerning the perception of dyspnea during changes in airway caliber provoked in the laboratory setting, but studies of asthma exacerbation are scarce. OBJECTIVE: To investigate whether the perception of dyspnea during histamine-induced bronchoconstriction might be used to identify patients with asthma who sense dyspnea poorly during exacerbation. METHODS: The perception of dyspnea in 50 patients (45 female, 5 male) with asthma was evaluated at admission with exacerbation and during a stable period. Perceived intensity of dyspnea was estimated using a modified Borg scale. The perception of dyspnea in the stable period 4 to 6 weeks after exacerbation was measured with the histamine challenge test. Perception parameters were defined as the change in Borg score divided by the change in forced expiratory volume in 1 second (FEV1) as a percentage of the baseline FEV1 (deltaBorg/deltaFEV1) and as the Borg score at 20% decrease (PS20Histamine) or increase (PS20Exacerbation) in FEV1. RESULTS: The perception of dyspnea during asthma exacerbation was unrelated to the perception of dyspnea during histamine-induced bronchoconstriction (for deltaBorg/deltaFEV1, beta = .08, P = .50; for PS20, beta = -.11, P = .40). The kappa value for the agreement of poor perceivers at exacerbation and during the stable period was -0.21 (P = .10). However, the intensity of dyspnea caused by histamine-induced bronchoconstriction was lower than that caused by asthma exacerbation (PS20: 1.6 +/- 1.1 vs 2.8 +/- 2.5, respectively, P = .004; deltaBorg/deltaFEV1: 0.08 +/- 0.05 vs 0.21 +/- 0.28, respectively, P = .001). CONCLUSION: The perception of dyspnea during asthma exacerbation is not correlated with the perception of dyspnea during histamine-induced bronchoconstriction. Therefore, the perception of dyspnea during histamine-induced bronchoconstriction cannot be used to identify the asthmatic patients who perceive dyspnea poorly.

Adult↗

PubMed1999

Interleukin-8 inhalation directly provokes bronchoconstriction in guinea pigs.

BACKGROUND: Although it has been reported that the concentration of interleukin (IL)-8 in nasal lavage fluid and sputum and its production in bronchial epithelium were increased in asthmatic subjects, the direct effects of IL-8 on the airways in vivo is unclear. METHODS: We examined bronchoconstriction in response to IL-8 inhalation through an endotracheal cannula in anesthetized, artificially ventilated guinea pigs. RESULTS: Inhalation of IL-8 at concentrations of 1 and 10 microg/ml caused significant bronchoconstriction, as revealed by the elevation of pressure at the airway opening. Moreover, the bronchoconstriction induced by IL-8 was significantly inhibited by the antihistamines diphenhydramine and terfenadine, suggesting the involvement of histamine release in the IL-8-induced bronchoconstriction. No significant leukocyte infiltration was observed in the bronchoalveolar lavage fluid or histologic findings 25 min after the first IL-8 inhalation. CONCLUSIONS: IL-8 provokes bronchoconstriction without leukocyte accumulation in the airways, mediated in part by histamine release, in guinea pigs.

Administration, Inhalation↗

PubMed2001

Spasmolytic effect of magnesium sulfate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

BACKGROUND: Magnesium (Mg2+) has relaxant effects on histamine-induced bronchoconstriction. In addition, Mg2+ has been reported to reduce vascular smooth muscle tone and be clinically useful for treatment of persistent pulmonary hypertension of the newborn. In this study, we evaluated the relaxant effect of Mg2+ on serotonin (5HT)-induced bronchoconstriction and pulmonary hypertension. METHODS: Seven mongrel dogs were anesthetized with pentobarbital (30 mg x kg(-1) + 2 mg x kg(-1) x h(-1)) and paralyzed by pancuronium (0.2 mg x kg(-1) x h(-1)). Bronchoconstriction and pulmonary hypertension were elicited with 5HT (10 microg x kg(-1) + 1 mg x kg(-1) x h(-1)). Airway caliber was evaluated by changes in bronchial cross-sectional area (BCA) of the 3rd bronchial bifurcation measured by a fiberoptic bronchoscope method as previously reported. Pulmonary hypertension was assessed by changes in pulmonary vascular resistance (PVR). The BCA and PVR were expressed as per cent of the basal level. Thirty minutes after start of 5HT infusion, magnesium sulfate (MgSO4): 0 (saline), 1, 10, 100 and 1000 micromol x kg(-1) was given i.v.. Arterial blood was also collected to measure plasma level of Mg2+ and catecholamines. RESULTS: 5HT increased %PVR to 163+/-25% and decreased % BCA by 39.2+/-4.5%. Plasma level of Mg2+ following MgSO4 1000 micromol x kg(-1) i.v. exceeded its toxic level. The ED50s of MgSO4 (dose producing 50% relaxation of maximal constriction) was 47.8 micromol x kg(-1) and 1.09 mmol x kg(-1) for pulmonary hypertension and bronchoconstriction, respectively. The ratio of %PVR to %SVR was about 1.0 after MgSO4 0-100 micromol x kg(-1) i.v., although the ratio significantly increased after 1000 micromol x kg(-1) i.v.. CONCLUSION: In dogs, 5HT-induced pulmonary hypertension but not bronchoconstriction was significantly reduced by an iv bolus of MgSO4, resulting in a plasma concentration within the assumed therapeutic level.

Animals↗

PubMed1998

The effects of a novel sulphidopeptide leukotriene antagonist, BAY x7195, against elicited bronchoconstriction in the anaesthetized guinea-pig.

1. The novel leukotriene antagonist Bay x7195, has been evaluated against bronchoconstriction induced by leukotriene D4 (LTD4), the thromboxane A2 (TXA2) mimetic U46619, histamine and antigen, in the guinea-pig in vivo by use of a modified Konzett-Rössler preparation. 2. LTD4, given intravenously (i.v.) at 1 or 3 microg kg(-1) in the presence of indomethacin and sotalol, caused a 50-70% maximal bronchoconstriction in most animals. 3. BAY x7195, given i.v., orally (p.o.), by aerosol or dry powder insufflation, in lactose, reduced LTD4-induced bronchoconstriction dose-dependently. The approximate ID50 values were 83 microg kg(-1), 3 mg kg(-1), 0.0003% w/v for 20 breaths and 20 microg respectively. 4. The action of BAY x7195 (10 mg kg(-1), p.o.) was long lasting, causing significant inhibition of the LTD4-induced response (88% reduction) 8 h after dosing. 5. When given intravenously, in the presence of selected antagonists, BAY x7195 caused a dose-related reduction in the antigen-induced response, with an approximate ID50 of 2 mg kg(-1). 6. At 3 mg kg(-1), i.v., a dose which abolished the response to LTD4, BAY x7195 had no effect on U46619- or histamine-induced bronchoconstriction. 7. BAY x7195 is a potent, selective and long acting antagonist of LTD4-induced bronchoconstriction, in an anaesthetized, ventilated guinea-pig model. It is therefore worthy of clinical evaluation in diseases believed to involve the sulphidopeptide leukotrienes, such as asthma.

Administration, Oral↗

PubMed1999

Anaphylactic bronchoconstriction in BP2 mice: interactions between serotonin and acetylcholine.

1. Immunized BP2 mice developed an acute bronchoconstriction in vivo and airway muscle contraction in vitro in response to ovalbumin (OA) and these contractions were dose dependent. 2. Methysergide or atropine inhibited OA-induced bronchoconstriction in vivo and airway muscle contraction in vitro. 3. Neostigmine potentiated the OA-induced bronchoconstriction in vivo and airway muscle contraction in vitro of BP2 mice. This potentiation was markedly reduced by the administration of methysergide or atropine and when the two antagonists were administered together, the responses were completely inhibited. 4. Neostigmine also potentiated the serotonin (5-HT)- and acetylcholine (ACh)-induced bronchoconstriction and this potentiation was significantly reversed by atropine. 5. These results indicate that OA provokes a bronchoconstriction in immunized BP2 mice by stimulating the release of 5-HT, which in turn acts via the cholinergic mediator, ACh.

Acetylcholine↗

PubMed2002

Effect of ozagrel hydrochloride, a thromboxane synthetase inhibitor, on alcoholic beverage-induced bronchoconstriction in asthmatic patients.

Acetaldehyde is thought to be a main factor of alcohol-induced asthma. The thromboxane (TX) synthetase inhibitor, ozagrel hydrochloride, inhibits acetaldehyde-induced bronchoconstriction in asthmatic patients. The present study evaluated the involvement of TXA(2) on alcoholic beverage-induced bronchoconstriction. Four patients with alcohol-induced asthma received ozagrel (400 mg for 4 days) or placebo using a single-blind, randomized, cross-over design. On two separate study days, each subject drank the same brand and volume of alcoholic beverage (beer or Japanese sake) and bronchoconstriction was assessed as the change in peak expiratory flow (PEF). The effect of ozagrel on the aerosolized challenge of acetaldehyde was investigated in the same subjects. Although aerosolized acetaldehyde-induced bronchoconstriction was significantly prevented by ozagrel, there were no differences in the time course of the decrease in PEF or the maximum fall in PEF after alcohol intake between placebo and ozagrel. We conclude that TXA(2) is not involved in alcoholic beverage-induced bronchoconstriction.

Acetaldehyde↗

PubMed2006

Cardiopulmonary exercise testing in children and adolescents with asthma who report symptoms of exercise-induced bronchoconstriction.

Patients with asthma often report symptoms of exercise-induced bronchoconstriction. We performed cardiopulmonary exercise testing to establish the cause of exercise limitation in patients with asthma, under treatment, who reported symptoms of exercise-induced bronchoconstriction. Ten of the 42 patients meeting criteria for inclusion in our study (24%) developed exercise-induced bronchoconstriction. Exercise limitation without exercise-induced bronchoconstriction was found in both obese and non-obese patients, suggesting that poor fitness is a problem independent of body habitus. Including cardiopulmonary exercise testing in the management of children with suspected exercise-induced bronchoconstriction would provide a better understanding of the etiology of their symptoms and facilitate more appropriate treatment.

Adolescent↗

PubMed2003

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs.

BACKGROUND: Thiopental sometimes causes bronchospasm during induction of anaesthesia. In addition, we have reported previously that thiopental produced transient bronchospasm, which was blocked by atropine pretreatment, and worsened histamine-induced bronchoconstriction in dogs. Previous in vitro reports suggest that synthesis of contractile cyclooxygenase products, such as thromboxane A(2), may be involved in the mechanism of bronchospasm. However, the in vivo spastic effects have not been defined comprehensively. METHODS: Twenty-seven mongrel dogs were anaesthetized with pentobarbital. Bronchoconstriction was elicited with methacholine (0.5 microg kg(-1)+5.0 microg kg(-1) min(-1); Mch group, n=7) or serotonin (10 microg kg(-1)+1 mg kg(-1) h(-1); 5HT group, n=20), and assessed as percentage changes in bronchial cross-sectional area (BCA, basal=100%) using a bronchoscope. In the 5HT group, dogs were subdivided into four groups of five each: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HT groups, 30 min before serotonin infusion dogs were given saline and indomethacin respectively at 5 mg kg(-1) i.v. In all groups, 30 min after bronchoconstrictor infusion started, dogs were given thiopental at doses between 0 (saline) and 20 mg kg(-1). In the 5HT-S and 5HT-A groups, dogs were given saline or atropine 0.2 mg kg(-1) i.v. 5 min after thiopental 20 mg kg(-1). RESULTS: Methacholine and serotonin reduced BCA by about 50 and 40% respectively. Thiopental 20 mg kg(-1) increased and decreased BCA by about 20 and 10% in the Mch and 5HT groups respectively. Indomethacin and atropine did not attenuate the potentiation of serotonin bronchoconstriction produced by thiopental. CONCLUSION: The present study indicates that thiopental may attenuate or worsen bronchoconstriction induced by muscarinic or serotonin receptor stimulation, respectively. The synthesis of contractile cyclooxygenase products and cholinergic stimulation may not be involved in the contractile effect of thiopental on serotonin bronchoconstriction.

Anesthetics, Intravenous↗

PubMed2004

Effects of the alpha2-adrenoceptor agonist dexmedetomidine on bronchoconstriction in dogs.

BACKGROUND: Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that alpha2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective alpha2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown. METHODS: After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 microg/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated. RESULTS: At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone). CONCLUSION: alpha2-Adrenoceptor stimulation with intravenous dexmedetomidine completely blocked histamine-induced bronchoconstriction in dogs. Therefore, dexmedetomidine might be beneficial to decrease airway reactivity in patients with chronic obstructive pulmonary disease or asthma, particularly during weaning from mechanical ventilation, when neurally mediated airway reflexes may be elicited.

Administration, Inhalation↗

PubMed2000

Ventilatory support by tracheal gas insufflation and chest vibration during bronchoconstriction.

OBJECTIVE: To determine whether chest wall vibration with tracheal gas insufflation during bronchoconstriction maintains gas exchange at lower airway and intrathoracic pressures than those that occur during positive pressure ventilation. DESIGN: Prospective study. SETTING: Experimental laboratory. SUBJECTS: Six anesthetized, paralyzed mongrel dogs (mean weight, 24.7+/-3.8 kg). INTERVENTIONS: Dogs were ventilated by two methods: mechanical ventilation (7 breaths/min, 25 mL/kg tidal volume); and tracheal oxygen insufflation at 0.15 L x kg(-1) x min(-1) delivered with external chest wall vibration (29 Hz, 2 mm amplitude) of the dependent hemithorax. Bronchoconstriction was induced by methacholine infusion adjusted to double and quadruple the baseline airway resistance. Proximal mean airway pressure was kept equal for both modes of ventilation. MEASUREMENTS AND MAIN RESULTS: Airway pressure and flow, esophageal pressure, hemodynamic variables (cardiac output, systemic and pulmonary arterial pressures, pulmonary artery occlusion pressure) and gas exchange variables (PaO2, PaCO2, pH, shunt fraction, VO2) were measured. Peak airway pressure was lower (p < .05) with insufflation and vibration than with mechanical ventilation by 83.6% at baseline resistance, by 76.9% at twice baseline resistance, and by 76.8% at four times baseline resistance. Peak esophageal pressure was lower (p < .05) during insufflation with vibration by 68.5% at baseline resistance, by 87.5% at twice baseline resistance, and by 107% at four times baseline resistance. During insufflation with vibration, mild hypercapnia (PaCO2 58+/-3 torr (7.7+/-0.4 kPa) and pH 7.28+/-0.02) developed with moderate bronchoconstriction; more profound respiratory acidosis (PaCO2 137+/-41 torr (18.2+/-5.5 kPa) and pH 6.87+/-0.11) developed with severe bronchoconstriction. CONCLUSIONS: Tracheal gas insufflation with chest vibration supports gas exchange with permissive hypercapnia only during moderate, not severe, bronchoconstriction. Gas exchange was achieved at lower airway and intrathoracic pressures than those that developed during mechanical ventilation. The alveolar hypoventilation that occurred during insufflation with vibration indicates impaired CO2 elimination and suggests increased resistance to CO2 transport. This ventilation technique may confer therapeutic advantages over mechanical ventilation in the treatment of asthma.

Animals↗

PubMed2001

Bronchoconstrictive and relaxant effects of lidocaine on the airway in dogs.

OBJECTIVE: Intravenous lidocaine commonly is used to treat ventricular arrhythmias and to attenuate reflex airway constriction and intracranial pressure elevation during airway manipulation in intensive care units. There is much controversy as to the actions of lidocaine on the airway, so the aim of this study was to compare, in detail, the actions of lidocaine with those of bupivacaine and procaine on airway caliber and the associated changes in plasma catecholamine concentrations in the dog. DESIGN: Prospective, randomized, controlled experimental in vivo and in vitro study. SETTING: A university research laboratory. SUBJECTS: Mongrel dogs. INTERVENTIONS: In the first experiment, we evaluated the effects of intravenous local anesthetics--lidocaine 0-10 mg/kg (n = 7), bupivacaine 0-2.5 mg/kg (n = 7), or procaine 0-20 mg/kg (n = 7)--on basal airway tone. In second experiment, histamine (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 6), serotonin (10 microg/kg + 500 microg x kg(-1) x hr(-1), n = 7), and methacholine (0.5 microg/kg + 300 microg x kg(-1) x hr(-1), n = 7) were infused to determine the effects of lidocaine (0-10 mg/kg) on agonist-induced bronchoconstriction. In addition, the actions of lidocaine on vagal nerve stimulation were examined (n = 7). MEASUREMENTS AND MAIN RESULTS: Bronchial cross-sectional area at the third bronchial bifurcation of dogs was monitored continuously through a fiberoptic bronchoscope. In the first experiment, all local anesthetics produced a dose-dependent decrease in basal bronchial cross-sectional area. In the second experiment, lidocaine significantly potentiated histamine and serotonin-induced bronchoconstriction. In contrast, lidocaine antagonized methacholine- and vagal nerve stimulation-induced bronchoconstriction. CONCLUSION: We have clearly demonstrated that lidocaine may produce direct bronchoconstriction and worsen some agonist-induced bronchoconstriction, but it prevents reflex airway constriction. Therefore, we suggest that this agent be used with caution in asthmatics.

Anesthetics, Local↗

PubMed1996

Aerosolized tachykinin antagonists inhibit pentamidine-induce bronchoconstriction in guinea pigs.

To investigate the role of tachykinins in pentamidine-induced bronchoconstriction and airway microvascular leakage in the guinea pig, we examined the effects on bronchoconstriction and microvascular leakage of the nonpeptide antagonists of NK1 and NK2 tachykinin-receptors, respectively, CP-96,345 and SR 48968. Respiratory system resistance was measured by the occlusion method in anaesthetized, tracheotomized and mechanically ventilated guinea pigs. Airway microvascular permeability was evaluated by measuring the quantity of Evans blue dye in the trachea and main bronchi. Aerosolized CP-96,345 or SR 48968 partially abolished pentamidine-induced bronchoconstriction (at 5 to 30 mg/mL pentamidine; 60 breaths) whereas the combination of the two prevented it. In contrast, CP-96,345 and SR 48968 did not prevent the increase in airway microvascular permeability induced by pentamidine (50 mg/mL; 90 breaths) whether they were administered separately or together, by aerosol or intravenously. These results demonstrate that in the guinea pig, pentamidine-induced bronchoconstriction is mediated through both NK1 and NK2 tachykinin-receptor activation and that when directly administered into the airways, tachykinin antagonists effectively prevent pentamidine-induced bronchoconstriction.

Aerosols↗

PubMed1991

5-Hydroxytryptamine-induced bronchoconstriction in the guinea-pig: effect of 5-HT2 receptor activation on acetylcholine release.

1. The bronchoconstrictor responses to 5-hydroxytryptamine (5-HT) were studied in the guinea-pig to establish whether they are partly attributable to parasympathetic activation within the airways. 5-HT dose-response curves were constructed in anaesthetized and ventilated guinea-pigs pretreated with saline, or by bilateral cervical vagotomy or vagotomy plus atropine 3 mg kg-1, i.v. Vagotomy had no effect on 5-HT-induced bronchoconstriction but vagotomy plus atropine significantly reduced it. 2. To determine whether parasympathetic activation within the airways resulted from pre- or postganglionic stimulation, 5-HT dose-response curves were constructed for two groups of vagotomized guinea-pigs treated with hexamethonium 2 mg kg-1, or hexamethonium 2 mg kg-1, plus atropine 3 mg kg-1. Guinea-pigs treated with hexamethonium plus atropine experienced significantly less 5-HT-induced bronchoconstriction than those treated with hexamethonium alone. 3. To characterize the subtype of 5-HT receptors involved in the activation of the parasympathetic system by 5-HT, dose-response curves to 5-HT were constructed for four groups of vagotomized guinea-pigs treated with saline, 1 mg kg-1 of the 5-HT3 antagonist ICS 205-930, or either 0.01 or 0.1 mg kg-1 of the 5-HT2 antagonist ketanserin. ICS 205-930 enhanced 5-HT-induced bronchoconstriction but 0.01 mg kg-1 ketanserin inhibited it significantly and 0.1 mg kg-1 ketanserin abolished it. To confirm the involvement of 5-HT2 receptors in these responses, we studied the effects in vagotomized guinea-pigs of atropine on the bronchoconstriction induced by the 5-HT2 agonist,x alpha-methyl-5-HT, infused at rates of 40 and 80ngkg-1s-'. At both rates, atropine significantly reduced the bronchoconstrictor responses to alpha-methyl-5-HT. 4. The above results indicate that 5-HT-induced bronchoconstriction is indeed partly mediated by parasympathetic activation within the airways. This activation is mediated by stimulation of 5-HT2 receptors which are probably located on the postganglionic parasympathetic nerve endings.

Acetylcholine↗

PubMed1992

Guinea-pig treatment with pertussis toxin suppresses macrophage-dependent bronchoconstriction by fMLP and fails to inhibit the effects of PAF.

1. Bronchoconstriction and thromboxane B2 (TxB2) release following the intra-tracheal administration of the secretagogue N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to lungs from pertussis toxin-treated guinea-pigs in vivo and in vitro were inhibited as compared to saline-treated animals, under conditions where the responses to PAF were modified less effectively. 2. The cell target accounting for bronchoconstriction by fMLP and for inhibition by pertussis toxin is located in the airways and is probably the alveolar macrophage. Indeed (a) fMLP-induced superoxide anions and TxB2 formation by alveolar macrophages were inhibited by pertussis toxin given in vivo; (b) Gi proteins of membranes from alveolar macrophages were ADP-ribosylated in vivo by pertussis toxin and (c) bronchoconstriction and TxB2 release in response to the intra-tracheal administration of fMLP to lungs from pertussis toxin-treated animals were restored when alveolar macrophages from control guinea-pigs were transferred into the airways of pertussis toxin-treated animals before lung isolation. 3. Pertussis toxin administered to guinea-pigs in vivo, reduced the subsequent TxB2 formation and superoxide anion release by alveolar macrophages stimulated with PAF, but failed to inhibit PAF-induced bronchoconstriction. 4. Formation of TxB2 by alveolar macrophages following the intra-tracheal administration of fMLP accounts for bronchoconstriction and requires pertussis toxin-sensitive Gi proteins. PAF operates via a different mechanism, which is independent of Gi-like protein and involves mediators other than TxB2 and superoxide anions.

Adenosine Diphosphate Ribose↗

PubMed1991

Selectivity of ruthenium red in inhibiting bronchoconstriction and CGRP release induced by afferent C-fibre activation in the guinea-pig lung.

In the present study we evaluated the effects of ruthenium red, a blocker of transmembrane Ca2+ fluxes, on bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by different stimuli in the isolated perfused guinea-pig lung. Vagal stimulation (1 Hz, 1 min), capsaicin (10(-8) M, 10(-6) M), resiniferatoxin (3 x 10(-10) M), nicotine (10(-4) M), bradykinin (5 x 10(-6) M) and histamine (10(-5) M) evoked bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Ruthenium red (5 x 10(-6) M) almost completely inhibited the bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow induced by capsaicin and resiniferatoxin but did not influence the effects induced by vagal nerve stimulation, nicotine, bradykinin or histamine. The 20-deacetylated derivative of resiniferatoxin (ROPA), which lacks the homovanillyl ester group, did not evoke release or bronchoconstriction. Ruthenium red (3 x 10(-4) M) aerosol attenuated the cough induced by nebulized citric acid in conscious guinea-pigs. Citric acid-induced coughing is mediated via capsaicin-sensitive neurons. However, cigarette smoke-induced coughing, which involves capsaicin-resistant mechanisms, was not affected by ruthenium red. In conclusion, ruthenium red selectively inhibits the capsaicin, resiniferatoxin and citric acid-induced excitation of the sensory nerves as revealed by calcitonin gene-related peptide-like immunoreactivity release, bronchoconstriction and coughing, suggesting that these agents share a common mechanism of action.

Animals↗

PubMed2005

MEN16132, a novel potent and selective nonpeptide kinin B2 receptor antagonist: in vivo activity on bradykinin-induced bronchoconstriction and nasal mucosa microvascular leakage in anesthetized guinea pigs.

We have tested the activity of 4-(S)-amino-5-(4-[4-[2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido]-tetrahydro-2H-4-pyranylcarbonyl] piperazino)-5-oxopentyl](trimethyl)ammonium chloride hydrochloride (MEN16132), a novel nonpeptide kinin B(2) receptor antagonist, on bradykinin (BK)-induced inflammatory responses, bronchoconstriction, and hypotension in guinea pigs. After i.v. (1-10 nmol/kg i.v.), intratracheal (i.t.) (10-100 nmol/kg i.t.), or aerosol (0.01-0.1 mM/5 min) administration, MEN16132 inhibited in a dose-dependent manner the bronchoconstriction induced by BK (10 nmol/kg i.v.). MEN16132 was more potent and possessed a longer duration of action as compared with the peptide B(2) receptor antagonist icatibant (HOE140; H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH trifluoroacetate). After i.v. administration, its inhibitory effect on bronchoconstriction lasted more than 8 h at 30 nmol/kg. When administered by i.v. or i.t. routes, the dose completely inhibiting bronchoconstriction also partially reduced the hypotensive response to BK, whereas after aerosol administration, the inhibitory effect was limited to respiratory level. Intranasal (i.n.) administration of MEN16132 (0.01-0.3 nmol/nostril) reduced, in a dose-dependent and long-lasting manner, the nasal mucosa plasma protein extravasation induced by BK (100 nmol/nostril), and it exerted a complete inhibition at about 30-fold lower dose than icatibant. At 1 nmol/nostril, MEN16132 activity was significant for at least 6 h with no systemic effect measured as inhibition of BK-induced hypotension, and at 10 nmol/nostril, the inhibitory effect lasted for more than 15 h with only a weak effect on hypotension. These findings indicate that in vivo MEN16132 is a potent kinin B(2) receptor antagonist with long duration of action, both after i.v. and local administration. A complete and prolonged inhibition of BK-induced bronchoconstriction or nasal inflammation can be achieved with MEN16132 topical administration (aerosol or i.n.) at doses devoid of systemic effects.

Anesthesia↗