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Eiji Nakano - One of the best experts on this subject based on the ideXlab platform.

  • Airway Constriction by xanthine xanthine oxidase in guinea pigs in vivo
    Journal of Toxicology and Environmental Health, 1993
    Co-Authors: Miwa Misawa, Eiji Nakano
    Abstract:

    Reactive oxygens are considered to be one of the mediators involved in inflammation. We investigated the constrictive effects of reactive oxygens generated by aerosolized xanthine/xanthine oxidase (XOD) on the Airways of anesthetized guinea pigs. Airway resistance was measured with a modified Konzett‐Rossler method and expressed as a change in ventilation overflow (VO). Inhalation ofxanthine (1.0 M)/XOD (10, 15 U/ml) caused a significant increase in VO. This Airway Constriction tended to be enhanced by pretreatment with inhaled superoxide dismutase, but was suppressed by inhaled catalase. Inhalation of hydrogen peroxide caused an Airway Constriction in a concentration‐dependent manner (0.1–2.0 M). Xanthine/XOD significantly enhanced the maximal change in VO after inducing Airway inflammation by SO2 exposure. The pretreatment with inhalation of xanthine/XOD did not affect the Airway Constriction induced by inhaled histamine. However, in SO2‐exposed guinea pigs, the inhalation of xanthine/XOD significantly ...

  • Airway Constriction by xanthine/xanthine oxidase in guinea pigs in vivo.
    Journal of Toxicology and Environmental Health, 1993
    Co-Authors: Miwa Misawa, Eiji Nakano
    Abstract:

    Reactive oxygens are considered to be one of the mediators involved in inflammation. We investigated the constrictive effects of reactive oxygens generated by aerosolized xanthine/xanthine oxidase (XOD) on the Airways of anesthetized guinea pigs. Airway resistance was measured with a modified Konzett‐Rossler method and expressed as a change in ventilation overflow (VO). Inhalation ofxanthine (1.0 M)/XOD (10, 15 U/ml) caused a significant increase in VO. This Airway Constriction tended to be enhanced by pretreatment with inhaled superoxide dismutase, but was suppressed by inhaled catalase. Inhalation of hydrogen peroxide caused an Airway Constriction in a concentration‐dependent manner (0.1–2.0 M). Xanthine/XOD significantly enhanced the maximal change in VO after inducing Airway inflammation by SO2 exposure. The pretreatment with inhalation of xanthine/XOD did not affect the Airway Constriction induced by inhaled histamine. However, in SO2‐exposed guinea pigs, the inhalation of xanthine/XOD significantly ...

Stefan Hippenstiel - One of the best experts on this subject based on the ideXlab platform.

  • spleen tyrosine kinase inhibition blocks Airway Constriction and protects from th2 induced Airway inflammation and remodeling
    Allergy, 2017
    Co-Authors: Christoph Tabeling, J Herbert, Andreas C Hocke, David J Lamb, Stefanlutz Wollin, E Boiarina, H Movassagh, J Scheffel, J M Doehn, Stefan Hippenstiel
    Abstract:

    Background Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic Airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on Airway Constriction independent of allergen sensitization remain elusive. Methods Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression. The effects of prophylactic or therapeutic Syk inhibition on allergic Airway inflammation, hyperresponsiveness and Airway remodeling were analyzed in allergen-sensitized and Airway-challenged mice. The effects of Syk inhibitors BAY 61-3606 or BI 1002494 on Airway function were investigated in isolated lungs of wild-type, PKCα-deficient, mast cell-deficient or eNOS-deficient mice. Results Syk expression was found in human and murine Airway smooth muscle cells. Syk inhibition reduced allergic Airway inflammation, Airway hyperresponsiveness and pulmonary collagen deposition. In naive mice, Syk inhibition diminished Airway responsiveness independently of mast cells, or PKCα or eNOS expression and rapidly reversed established bronchoConstriction independently of NO. Simultaneous inhibition of Syk and PKC revealed additive dilatory effects, whereas combined inhibition of Syk and rho kinase or Syk and p38 MAPK did not cause additive bronchodilation. Conclusions Syk inhibition directly attenuates Airway smooth muscle cell contraction independent of its protective immunomodulatory effects on allergic Airway inflammation, hyperresponsiveness and Airway remodeling. Syk mediates bronchoConstriction in a NO-independent manner, presumably via rho kinase and p38 MAPK, and Syk inhibition might present a promising therapeutic approach in chronic asthma as well as acute asthma attacks. This article is protected by copyright. All rights reserved.

Wayne Mitzner - One of the best experts on this subject based on the ideXlab platform.

  • assessment of heterogeneous Airway Constriction in dogs a structure function analysis
    Journal of Applied Physiology, 2009
    Co-Authors: David W Kaczka, Robert H. Brown, Wayne Mitzner
    Abstract:

    Obstructive lung diseases are often characterized by heterogeneous patterns of bronchoConstriction, although specific relationships between structural heterogeneity and lung function have yet to be...

  • duration of deep inspiration and subsequent Airway Constriction in vivo
    Journal of Asthma, 2003
    Co-Authors: Robert H. Brown, Wayne Mitzner
    Abstract:

    The effects of a deep inspiration (DI) in asthmatics differ from those observed in healthy subjects. When considering the effects of a DI, an implicit assumption is that all the Airways are distending at the same rate as the lung parenchyma. However, with such rapid lung inflation, the ability of contracted Airways to dynamically follow the lung parenchyma was recently shown to significantly lag the lung inflation. Another potentially important variable in the response of the individual Airways to a DI that has not been well studied is the duration of the DI maneuver. The current study examines the effects of increasing duration at TLC during a DI on subsequent Airway caliber. In five anesthetized and ventilated mongrel dogs, after DIs of increasing duration, changes in Airway size were measured over the subsequent 5-minute period using high-resolution computed tomography. Results show that the duration of the maneuver is extremely important, leading to a qualitative change in the Airway response. A long ...

  • effects of tidal volume stretch on Airway Constriction in vivo
    Journal of Applied Physiology, 2001
    Co-Authors: Robert H. Brown, Wayne Mitzner
    Abstract:

    Tidal stresses are thought to be involved in maintaining Airway patency in vivo. The present study examined the effects of normal stresses exerted by the lung parenchyma during tidal ventilation on recovery from agonist-induced Airway Constriction. In seven anesthetized dogs, one lung was selectively ventilated with a Univent endotracheal tube (Vitaid, Lewiston, NY). Airway tone was increased either transiently (intravenous bolus) or continuously (intravenous infusion) with methacholine (MCh). During one-lung ventilation, changes in the Airway size of both lungs were measured for up to 40 min during recovery from Constriction by using high-resolution computed tomography. After recovery to baseline, the alternate lung was ventilated, and the protocol was repeated. The absence of tidal stresses led to an attenuated recovery from either transient or steady-state Airway Constriction. The effectiveness or lack thereof of normal tidal stress in stabilizing Airway size may be one factor that contributes to the lack of reversal with tidal breathing and deep inspiration seen in asthmatic subjects.

  • Spontaneous Airways Constrict During Breath Holding Studied by High-Resolution Computed Tomography
    Chest, 1994
    Co-Authors: Robert H. Brown, Elias A. Zerhouni, Christian J Herold, Wayne Mitzner
    Abstract:

    Airway Constriction during a breath hold could not be examined previously using standard methods. We used high-resolution computed tomography (HRCT) in vivo to assess the temporal changes in Airway area and the effects of a deep inspiration with and without vagal suppression. Five dogs were anesthetized, intubated, and their lungs ventilated with 100 percent oxygen. Fifteen HRCT slices were obtained at functional residual capacity (FRC) either immediately after stopping ventilation at end expiration after either a tidal volume breath or three deep inspirations. Subsequently the dogs were given atropine, 0.2 mg/kg, and the scans were repeated. The cross-sectional areas of 33 Airways ranging in size from 1.6 to 9.7 mm in diameter were measured. Airways were separated in three groups based on size: small ( 6 mm in diameter). The small, medium, and large Airways showed a spontaneous Constriction over time to 49 ± 8 percent, 83 ± 4 percent, and 82 ± 4 percent of initial Airway size, respectively (p in vivo , we found that Airways spontaneously constrict during a prolonged expiratory pause, and a deep inspiration significantly augments this Airway Constriction. These responses are mediated via vagal afferent pathways, likely arising from progressively decreasing slow-adapting receptor activity.

  • bronchial circulatory reversal of methacholine induced Airway Constriction
    Journal of Applied Physiology, 1990
    Co-Authors: Elizabeth M Wagner, Wayne Mitzner
    Abstract:

    Although a role for the bronchial circulation in clearance of bronchoactive agents has been frequently proposed, experimental evidence is limited. In this study, we determined the importance of bronchial blood flow (QBA) in the recovery from methacholine-(MCh) induced bronchoConstriction. In 10 pentobarbital-anesthetized ventilated sheep, the bronchial branch of the bronchoesophageal artery was cannulated and perfused (0.7 ml.min-1.kg-1) with blood pumped from the femoral artery. MCh was infused directly into the bronchial artery at increasing concentrations (10(-7) to 10(-5) M). MCh infusion caused a concentration-dependent increase in Airway resistance at constant QBA. However, the time constant of recovery (TC) from Airway Constriction after cessation of the MCh infusion was not dependent on the MCh concentration or the magnitude of the increases in Airway resistance. When QBA was at 50, 100, and 200% of control level, with constant MCh concentration, TC was 44 +/- 6, 25 +/- 2, and 24 +/- 2 (SE) s at each flow level, respectively. TC at 50% of control QBA was significantly greater than at control QBA (P less than 0.01). Thus the magnitude of QBA can alter the time course of recovery from MCh-induced increases in Airway resistance. These results document the importance of QBA in reversing agonist-induced Constriction and suggest that an impaired bronchial circulation may contribute to the mechanism of Airway hyperreactivity.

Fungjou Lu - One of the best experts on this subject based on the ideXlab platform.

  • mast cells and reactive oxygen species in citric acid induced Airway Constriction
    Journal of Applied Physiology, 2004
    Co-Authors: Liling Wu, Fungjou Lu
    Abstract:

    The noncholinergic Airway Constriction is mediated by tachykinins, mainly neurokinin A and substance P, and this bronchoConstriction is usually enhanced during inflammatory episodes. We demonstrated previously that reactive oxygen species play an important role in capsaicin-, hyperventilation-, and citric acid (CA) inhalation-induced noncholinergic Airway Constriction. For understanding cellular involvement, we further investigated the relationship between mast cells, bradykinin (BK), reactive oxygen species, and noncholinergic Airway Constriction. Sixty-five guinea pigs were divided into seven groups: saline control; CA; BK + CA; cromolyn sodium (CS) + CA; BK + CS + CA; compound 48/80 + CA; and compound 48/80 + BK + CA. CS was used to stabilize mast cells, whereas a secretagogue, compound 48/80, was for the depletion of mast cells. Each animal was anesthetized, cannulated, paralyzed, and ventilated artificially. In control animals, CA aerosol inhalation caused decreases in dynamic compliance and forced e...

  • roles of oxygen radicals and elastase in citric acid induced Airway Constriction of guinea pigs
    British Journal of Pharmacology, 1999
    Co-Authors: Wenyi Chiou, Fungjou Lu, Long Y Chiang
    Abstract:

    Antioxidants attenuate noncholinergic Airway Constriction. To further investigate the relationship between tachykinin-mediated Airway Constriction and oxygen radicals, we explored citric acid-induced bronchial Constriction in 48 young Hartley strain guinea-pigs, divided into six groups: control; citric acid; hexa(sulphobutyl)fullerenes+citric acid; hexa(sulphobutyl)fullerenes+phosphoramidon+citric acid; dimethylthiourea (DMTU)+citric acid; and DMTU+phosphoramidon+citric acid. Hexa(sulphobutyl)fullerenes and DMTU are scavengers of oxygen radicals while phosphoramidon is an inhibitor of the major degradation enzyme for tachykinins. Animals were anaesthetized, paralyzed, and artificially ventilated. Each animal was given 50 breaths of 4 ml saline or citric acid aerosol. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 (FEV0.1), and maximal expiratory flow at 30% total lung capacity (V[dot above]max30) to evaluate the degree of Airway Constriction. Citric acid, but not saline, aerosol inhalation caused marked decreases in Crs, FEV0.1 and V[dot above]max30, indicating marked Airway Constriction. This Constriction was significantly attenuated by either hexa(sulphobutyl)fullerenes or by DMTU. In addition, phosphoramidon significantly reversed the attenuating action of hexa(sulphobutyl)fullerenes, but not that of DMTU. Citric acid aerosol inhalation caused increases in both lucigenin- and t-butyl hydroperoxide-initiated chemiluminescence counts, indicating citric acid-induced increase in oxygen radicals and decrease in antioxidants in bronchoalveolar lavage fluid. These alterations were significantly suppressed by either hexa(sulphobutyl)fullerenes or DMTU. An elastase inhibitor eglin-c also significantly attenuated citric acid-induced Airway Constriction, indicating the contributing role of elastase in this type of Constriction. We conclude that both oxygen radicals and elastase play an important role in tachykinin-mediated, citric acid-induced Airway Constriction. British Journal of Pharmacology (1999) 126, 778–784; doi:10.1038/sj.bjp.0702352

Akitomo Matsuki - One of the best experts on this subject based on the ideXlab platform.

  • effects of three different l type ca2 entry blockers on Airway Constriction induced by muscarinic receptor stimulation
    BJA: British Journal of Anaesthesia, 2003
    Co-Authors: Kazuyoshi Hirota, Eiji Hashiba, H Yoshioka, S Kabara, Akitomo Matsuki
    Abstract:

    Background The crucial role of L-type Ca2+ channels in Airway smooth muscle contraction suggests that these channels could be an important therapeutic target. There are three separate drug binding sites on this channel: those for dihydropyridines, benzothiazepines and phenyl alkylamines. In this study, we examined the effects of the dihydropyridines nifedipine and nicardipine, the benzothiazepine diltiazem, and the phenylalkylamine verapamil on Airway Constriction. Methods Tension of guinea-pig tracheal strips was measured isometrically in vitro with a force displacement transducer. Strips were precontracted with carbachol 10−7 M with or without 4-aminopyridine 10−3 M, a voltage-sensitive K+channel blocker. Then, nifedipine 10−8–10−4 M, diltiazem 10−8–3×10−4 M or verapamil 10−8–3×10−4 M was added cumulatively to the organ bath (n=6 each). The bronchial cross-sectional area of pentobarbital-anaesthetized dogs was assessed using a bronchoscopy method. BronchoConstriction was elicited with methacholine 0.5 µg kg−1 plus 5 µg kg−1 min−1, and then nicardipine 0–1000 µg kg−1, diltiazem 0–3000 µg kg−1 or verapamil 0–3000 µg kg−1 were given i.v. (n=7 each). Results In the in vitro experiments, nifedipine and diltiazem fully reversed carbachol-mediated tracheal contraction with logIC50 values of 4.76 ( sem 0.22) (mean 17.5 µM) and 4.60 (0.33) (mean 24.8 µM), respectively. Although verapamil 10−6–10−4 M reversed the contraction by 87.2%, strip tension re-increased by 18.1% following maximal relaxation with verapamil 3×10−4M. This re-increase was almost fully abolished by pretreatment with 4-aminopyridine. In the in vivo experiments, nicardipine and diltiazem dose-dependently reversed methacholine-induced bronchoConstriction, with logID50 values of 3.22 (0.05) (mean 0.60 mg kg−1) and 1.85 (0.32) (mean 14.0 mg kg−1), respectively. Verapamil worsened methacholine-induced bronchoConstriction. Conclusions Although supraclinical doses of dihydropyridines and benzothiazepines can produce Airway relaxant effects, these agents are unlikely to be used in the treatment of bronchoConstriction. In addition, verapamil may aggravate Airway Constriction. Br J Anaesth 2003; 90: 671–5

  • Effects of three different L‐type Ca2+ entry blockers on Airway Constriction induced by muscarinic receptor stimulation
    BJA: British Journal of Anaesthesia, 2003
    Co-Authors: Kazuyoshi Hirota, Eiji Hashiba, H Yoshioka, S Kabara, Akitomo Matsuki
    Abstract:

    Background The crucial role of L-type Ca2+ channels in Airway smooth muscle contraction suggests that these channels could be an important therapeutic target. There are three separate drug binding sites on this channel: those for dihydropyridines, benzothiazepines and phenyl alkylamines. In this study, we examined the effects of the dihydropyridines nifedipine and nicardipine, the benzothiazepine diltiazem, and the phenylalkylamine verapamil on Airway Constriction. Methods Tension of guinea-pig tracheal strips was measured isometrically in vitro with a force displacement transducer. Strips were precontracted with carbachol 10−7 M with or without 4-aminopyridine 10−3 M, a voltage-sensitive K+channel blocker. Then, nifedipine 10−8–10−4 M, diltiazem 10−8–3×10−4 M or verapamil 10−8–3×10−4 M was added cumulatively to the organ bath (n=6 each). The bronchial cross-sectional area of pentobarbital-anaesthetized dogs was assessed using a bronchoscopy method. BronchoConstriction was elicited with methacholine 0.5 µg kg−1 plus 5 µg kg−1 min−1, and then nicardipine 0–1000 µg kg−1, diltiazem 0–3000 µg kg−1 or verapamil 0–3000 µg kg−1 were given i.v. (n=7 each). Results In the in vitro experiments, nifedipine and diltiazem fully reversed carbachol-mediated tracheal contraction with logIC50 values of 4.76 ( sem 0.22) (mean 17.5 µM) and 4.60 (0.33) (mean 24.8 µM), respectively. Although verapamil 10−6–10−4 M reversed the contraction by 87.2%, strip tension re-increased by 18.1% following maximal relaxation with verapamil 3×10−4M. This re-increase was almost fully abolished by pretreatment with 4-aminopyridine. In the in vivo experiments, nicardipine and diltiazem dose-dependently reversed methacholine-induced bronchoConstriction, with logID50 values of 3.22 (0.05) (mean 0.60 mg kg−1) and 1.85 (0.32) (mean 14.0 mg kg−1), respectively. Verapamil worsened methacholine-induced bronchoConstriction. Conclusions Although supraclinical doses of dihydropyridines and benzothiazepines can produce Airway relaxant effects, these agents are unlikely to be used in the treatment of bronchoConstriction. In addition, verapamil may aggravate Airway Constriction. Br J Anaesth 2003; 90: 671–5