1. We have reported that the renin-angiotensin system is activated in acute asthma, and also by high-dose nebulized β2-agonists. The contribution of other possible stimuli such as hypoxia is unknown. The present study examined the effect of hypoxia alone and also combined with β2-agonists on the activity of the renin-angiotensin system.
2. In a double-blind crossover study, eight healthy subjects were randomized to inhale a hypoxic (FiO2 = 12%) or normoxic mixture for a period of 30 min, with either nebulized salbutamol (5 mg) or placebo administered into the circuit after 10 min. Plasma renin, angiotensin II and serum angiotensin-converting enzyme were measured at baseline and at intervals up to 2 h. Pulse rate and oxygen saturation were monitored continuously throughout the study.
3. After hypoxia alone, there was no change in the levels of plasma renin or angiotensin II. When salbutamol was added to the hypoxic mixture, there was a significant rise in plasma renin and angiotensin II [mean (SEM) maximal increase in angiotensin II of 5.6 (2.9)pg/ml and renin of 15.5 (6.3) μ-units/ml at 60 min, P < 0.05 compared with normoxia]. When salbutamol was administered in the normoxic mixture, plasma renin and angiotensin II also increased but this effect was similar to the effect of salbutamol in the hypoxic mixture. Serum angiotensin-converting enzyme levels were unaffected by hypoxia or salbutamol.
4. We conclude from these results that there is activation of the renin—angiotensin system in healthy subjects by salbutamol, but not hypoxia. In addition, the effect of salbutamol on the renin—angiotensin system is not influenced by the presence of hypoxia. As similar levels of hypoxia occur in acute exacerbations of asthma, it seems unlikely that hypoxia is contributing to activation of the renin—angiotensin system in acute severe asthma.