Role of Alveolar β2-Adrenergic Receptors on Lung Fluid Clearance and Exercise Ventilation in Healthy Humans

BACKGROUND: In experimental conditions alveolar fluid clearance is controlled by alveolar β(2)-adrenergic receptors. We hypothesized that if this occurs in humans, then non-selective β-blockers should reduce the membrane diffusing capacity (D(M)), an index of lung interstitial fluid homeostasis. Moreover, we wondered whether this effect is potentiated by saline solution infusion, an intervention expected to cause interstitial lung edema. Since fluid retention within the lungs might trigger excessive ventilation during exercise, we also hypothesized that after the β(2)-blockade ventilation increased in excess to CO(2) output and this was further enhanced by interstitial edema. METHODS AND RESULTS: 22 healthy males took part in the study. On day 1, spirometry, lung diffusion for carbon monoxide (DLCO) including its subcomponents D(M) and capillary volume (V(Cap)), and cardiopulmonary exercise test were performed. On day 2, these tests were repeated after rapid 25 ml/kg saline infusion. Then, in random order 11 subjects were assigned to oral treatment with Carvedilol (CARV) and 11 to Bisoprolol (BISOPR). When heart rate fell at least by 10 beats·min(−1), the tests were repeated before (day 3) and after saline infusion (day 4). CARV but not BISOPR, decreased D(M) (−13±7%, p = 0.001) and increased V(Cap) (+20±22%, p = 0.016) and VE/VCO(2) slope (+12±8%, p<0.01). These changes further increased after saline: −18±13% for D(M) (p<0.01), +44±28% for V(Cap) (p<0.001), and +20±10% for VE/VCO(2) slope (p<0.001). CONCLUSIONS: These findings support the hypothesis that in humans in vivo the β(2)-alveolar receptors contribute to control alveolar fluid clearance and that interstitial lung fluid may trigger exercise hyperventilation.