Airway Constriction by xanthine xanthine oxidase in guinea pigs in vivo

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.

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 …

spleen tyrosine kinase inhibition blocks Airway Constriction and protects from th2 induced Airway inflammation and remodeling

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.

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assessment of heterogeneous Airway Constriction in dogs a structure function analysis

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

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

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.