Study objective: We have previously described activation of the renin-angiotensin system (RAS) in acute severe asthma and have also reported activation of the RAS in normal subjects by single doses of nebulized β2-agonists. In the present study, we have examined the effect of single and multiple doses of nebulized albuterol on the activity of the RAS in mild asthma.
Design: Eight patients with mild asthma were studied. The effect of single and multiple doses of nebulized albuterol (5 mg) on the activity of the RAS was compared with that of placebo using a randomized, double-blind crossover study design. Nebulized drugs were administered at time 0 and 30 min.
Measurements: Plasma renin, angiotensin II (Ang II), and serum potassium levels were measured at baseline following a short rest, and thereafter at intervals up to 150 min.
Results: Renin levels increased after both the single (S) and double (D) nebulized doses of albuterol and were significantly greater than placebo at 30 min after S, and at 45 and 120 min after D. Plasma Ang II level also increased after S and D and was significantly greater than placebo at 30 and 45 min after S, and at 30 min and all timepoints thereafter following D. In addition, the effect of D was significantly greater than S at 45 min.
Conclusions: These results confirm that there is activation of the RAS in asthmatic subjects by single doses of nebulized β2-agonists and that repeated dosing with nebulized albuterol has further, additive effects on plasma Ang II levels. It therefore seems likely that these agents are contributing to activation of the RAS in acute asthma, although the exact clinical significance of these transient changes in plasma Ang II levels in asthma is at present unclear.