EFFECT OF HYPOXIA AND BETA(2)-AGONISTS ON THE ACTIVITY OF THE RENIN-ANGIOTENSIN SYSTEM IN NORMAL SUBJECTS

1. We have reported that the renin-angiotensin system is activated in acute asthma, and also by high-dose nebulized beta(2)-agonists. The co ntribution of other possible stimuli such as hypoxia is unknown, The p resent study examined the effect of hypoxia alone and also combined wi th beta(2)-agonists on the activity of the renin-angiotensin system. 2 . In a double-blind crossover study, eight healthy subjects were rando mized to inhale a hypoxic (FiO(2)=12%) or normoxic mixture for a perio d of 30min, with either nebulized salbutamol (5mg) or placebo administ ered into the circuit after 10min. Plasma renin, angiotensin II and se rum angiotensin-converting enzyme were measured at baseline and at int ervals up to 2h. Pulse rate and oxygen saturation were monitored conti nuously throughout the study. 3. After hypoxia alone, there was no cha nge in the levels of plasma renin or angiotensin II. When salbutamol w as added to the hypoxic mixture, there was a significant rise in plasm a 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)mu-units/ml at 60min, P<0 .05 compared with normoxia]. When salbutamol was administered in the n ormoxic mixture, plasma renin and angiotensin II also increased but th is effect was similar to the effect of salbutamol in the hypoxic mixtu re. Serum angiotensin-converting enzyme levels were unaffected by hypo xia or salbutamol. 4. We conclude from these results that there is act ivation of the renin-angiotensin system in healthy subjects by salbuta mol, but not hypoxia. In addition, the effect of salbutamol on the ren in-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.