The effect of acute alteration in oxygen tension on the bronchodilator response to salbutamol in vitro and in vivo in man

These studies examine the effect of acute hypoxia on airway smooth muscle relaxation in response to salbutamol in vitro in human isolated bronchi from non-asthmatics and in vivo in-patients with asthma. Isometric responses were measured from rings of human bronchi pre-constricted with methacholine under oxygen tensions of 95% (hyperoxia), 20% (normoxia) and 4% (hypoxia). Once contractions had plateaued, concentration - response curves were conducted to salbutamol (10(-9)-10(-4)M). Twelve stable asthmatic patients were studied in a randomised double blind fashion. On two study days following baseline measurements, patients were randomised to receive either oxygen (FiO(2) 1.0) or a hypoxic gas mixture (FiO(2) 0.15) followed by three incremental doses of nebulised salbutamol at 15 min intervals. On two further study days nebulised saline was administered instead of salbutamol. In isolated bronchi, salbutamol-induced relaxations were significantly (P < 0.001) greater in hyperoxia and normoxia (P < 0.01) when compared to hypoxia. Among patients with asthma no significant differences were found in the mean maximum % change in forced expiratory volume (FEV1) from baseline between the hypoxic and hyperoxic study days on which nebulised salbutamol was administered. We conclude that acute hypoxia attenuates airway smooth muscle relaxation in response to salbutamol in vitro but has no effect on salbutamol-induced bronchodilation in in-patients with asthma. (C) 2001 Academic Press.