Abstract
Chronic hypoxia results in pulmonary hypertension (PHT) and bronchial hyperresponsiveness (BHR) via the involvement of the vagal pathway and/or via airway and pulmonary vascular remodelling. We aimed at characterizing whether inhibiting these pathways protects PHT and lung functional changes following chronic hypoxia.
Rats were exposed for 21 days to: room air (C, n=9), hypoxia (11 % O2, HC, n=8), hypoxia with concomitant daily treatment with sildenafil (20 mg/day, HS, n=7) or an anticholinergic, tiotropium (18 µg/day, HT n=8). End-expiratory lung volume (EELV) was determined plethysmographically. Lung responsiveness was assessed by forced oscillations during iv methacholine provocation, and the equivalent dose causing 200% increase in airway resistance (ED200) was determined. The right ventricular hypertrophy (RVH)-index was calculated. The pulmonary arterial wall thickness [(Dex-Din)/Dex, AWT] was measured on lung sections.
Hypoxia led to PHT and increased EELV with no significant effect of any of the treatments, which in contrast prevented hypoxia-induced BHR (Figure).
These findings suggest that the pathophysiological mechanisms of the hypoxia-induced cardiovascular and lung functional changes are mainly dissociated. Stimulating the NO-pathway or inhibiting the vagal tone has a beneficial effect on BHR without preventing hypoxia induced PHT.
Grant support: OTKA K81179; ERS LTRF172-2011.
- © 2013 ERS
