Mechanisms for lung function impairment and airway hyperresponsiveness following chronic hypoxia in rats.
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.
Pediatric Anesthesia Unit, Geneva Children's Hospital, Geneva, Switzerland. walid.habre@hcuge.ch
Walid
W
Habre
Tibor Z
TZ
Jánosi
Fabienne
F
Fontao
Carole
C
Meyers
Gergely
G
Albu
Jean-Claude
JC
Pache
Ferenc
F
Peták
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000150:complications* / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008176:Lung Volume Measurements; D016210:Methacholine Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects
D016210:Methacholine Chloride