The Effect of Chronic Hypoxia on Endothelin Receptor Subtype-mediated Responses in Rat Isolated Airways

Clayton, R.A.E.; Nally, Jane E.; MacLean, Margaret R.; Thomson, Neil C.; McGrath, J.C.

doi:10.1006/pupt.1999.0200

Cited by 2 publications

(2 citation statements)

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“…pulmonary hypertension; bronchial hyperreactivity; hypoxemia; endexpiratory lung volume CHRONIC ALVEOLAR HYPOXIA IS often encountered in chronic pulmonary diseases, such as chronic obstructive pulmonary disease (COPD) (19) and sleep apnea syndrome (15). The pulmonary hypertension developing during chronic hypoxia (CH) (6,8,20) induces deleterious changes in the pulmonary microvasculature, which then affect the viscoelastic properties of the parenchyma (16,17). This pulmonary vascular and bronchial remodeling further deteriorate the lung function and, therefore, initiate a positive cascade mechanism, leading to a…”

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confidence: 99%

Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats

Habre¹,

Jánosi

Fontao

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Although chronic normobaric hypoxia (CH) alters lung function, its potential to induce bronchial hyperreactivity (BHR) is still controversial. Thus the effects of CH on airway and tissue mechanics separately and changes in lung responsiveness to methacholine (MCh) were investigated. To clarify the mechanisms, mechanical changes were related to end-expiratory lung volume (EELV), in vivo results were compared with those in vitro, and lung histology was assessed. EELV was measured plethysmographically in two groups of rats exposed to 21 days of CH (11% O(2)) or to normoxia. Total respiratory impedance was measured under baseline conditions and following intravenous MCh challenges (2-18 microg x kg(-1) x min(-1)). The lungs were then excised and perfused, and the pulmonary input impedance was measured, while MCh provocations were repeated under a pulmonary capillary pressure of 5, 10, and 15 mmHg. Airway resistance, tissue damping, and elastance were extracted from the respiratory impedance and pulmonary input impedance spectra. The increases in EELV following CH were associated with decreases in airway resistance, whereas tissue damping and elastance remained unaffected. CH led to the development of severe BHR to MCh (206 +/- 30 vs. 95 +/- 24%, P < 0.001), which was not detectable when the same lungs were studied in vitro at any pulmonary capillary pressure levels maintained. Histology revealed pulmonary arterial vascular remodeling with overexpression of alpha-smooth muscle actin antibody in the bronchial wall. These findings suggest that, despite the counterbalancing effect of the increased EELV, BHR develops following CH, only in the presence of intact autonomous nervous system. Thus neural control plays a major role in the changes in the basal lung mechanics and responsiveness following CH.

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confidence: 99%

Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats

Habre¹,

Jánosi

Fontao

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Previous studies that have evaluated the effect of CH on rat tracheal hyperresponsiveness produced conflicting results. Clayton et al (6,7) reported that CH attenuates contractile responses in rat airways in vitro, whereas Belouchi et al (1) indicated that CH increases calcium responses in rat tracheal myocytes. In the present study, we have reexamined the effect of CH on the mechanical activity of rat isolated tracheal muscle with special attention to the normalization of the isometric force, since CH may induce smooth muscle remodeling (10,14).…”

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confidence: 99%

Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity

Roux

Duvert

Marthan

2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Roux, Etienne, Michel Duvert, and Roger Marthan. Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity. Am J Physiol Lung Cell Mol Physiol 283: L628-L635, 2002. First published April 19, 2002 10.1152/ajplung.00387.2001.-This study investigated the interaction between exposure to air pollutants and chronic hypoxia (CH). We used a hypobaric chamber (14 days at barometric pressure 380 mmHg) to produce CH in rats. Exposure to various doses of acrolein or ozone did not modify the mechanical response to cholinergic agonists. Exposure to 3 M/min acrolein did not alter epithelium-free trachea responsiveness. In contrast, direct exposure of freshly isolated myocytes to 2 and 3 M/min acrolein enhanced the amplitude of the first intracellular [Ca 2ϩ ] rise in response to 0.1 M ACh and the calcium oscillation frequency in response to 10 M ACh. CH alone did not alter smooth muscle cross-sectional area (SMA) or epithelium-plus-submucosa thickness. CH decreased maximal contractile response (maximal force normalized to SMA) but increased sensitivity (pEC 50) to cholinergic agonists. We conclude that unlike in normoxic rats, exposure to air pollutants does not induce airway hyperresponsiveness in CH rats, although it increased calcium signaling. These results cannot be explained by change in smooth muscle accessibility, but may be linked to the effect of CH on calcium-contraction coupling.ozone; acrolein; smooth muscle; rat trachea; excitation-contraction coupling INHALATION OF AIR POLLUTANTS induces airway hyperresponsiveness and, therefore, poses a possible risk to human health, especially in patients whose airways are already compromised by preexisting pathologies such as asthma or chronic obstructive pulmonary disease (COPD) (8,9,11). Unlike the interaction between asthma and air pollution that has largely been investigated by epidemiological, clinical, as well as experimental studies (16,17,29), very little is known about the combined effect of air pollution and chronic hypoxia (CH), a condition that is frequently observed in patients suffering from COPD (21, 31). The effect of CH, per se, on airway responsiveness remains unclear, since very few experimental studies have addressed this issue (1, 6).We previously reported that ex vivo administration of a variety of gas pollutants, such as ozone or acrolein, to either human lung or rat isolated airways alters the subsequent in vitro mechanical response (2-4, 26, 29). This alteration is related to changes in calcium signaling at the site of the smooth muscle cell (15, 28). We have also developed an experimental model of CH using a hypobaric chamber and observed that CH modifies the mechanical response of isolated airways as a consequence of an effect on calcium signaling (1, 5).The aim of the present study was thus to investigate the interaction between CH and exposure to pollutants in rat isolated trachea. We examined the effect in CH rats of preexposure to ozone and acrolein on the contractile response to muscarinic stimulation i...

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The Effect of Chronic Hypoxia on Endothelin Receptor Subtype-mediated Responses in Rat Isolated Airways

Cited by 2 publications

References 11 publications

Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats

Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats

Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity

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