THE EFFECT OF NEBULIZED ALBUTEROL ON THE ACTIVITY OF THE RENIN-ANGIOTENSIN SYSTEM IN ASTHMA

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 beta(2)-agonists. In the present study, we have examined the effect o f single and multiple doses of nebulized albuterol on the activity of the RAS in mild asthma. Design: Eight patients with mild asthma were s tudied. The effect of single and multiple doses of nebulized albuterol (5 mg) on the activity of the RAS was compared with that of placebo u sing a randomized, double-blind crossover study design. Nebulized drug s were administered at time 0 and 30 min. Measurements: Plasma renin, angiotensin II (Ang II), and serum potassium levels were measured at b aseline following a short rest, and thereafter at intervals up to 150 min. Results: Renin levels increased after both the single (S) and dou ble (D) nebulized doses of albuterol and were significantly greater th an placebo at 30 min after S, and at 45 and 120 min after D. Plasma An g 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 timepoint s thereafter following D. In addition, the effect of D was significant ly greater than S at 45 min, Conclusions: These results confirm that t here is activation of the RAS in asthmatic subjects by single doses of nebulized beta(2)-agonists and that repeated dosing with nebulized al buterol has further, additive effects on plasma Ang II levels. It ther efore 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 presen t unclear.