Investigation of the mechanism of beta 2-agonist-induced activation of the renin-angiotensin system.
1. We have previously described activation of the renin-angiotensin system in asthma, and also by high-dose nebulized beta 2-agonists. In this study we sought to determine the mechanism responsible. 2. The influence of the angiotensin-converting enzyme inhibitor, lisinopril, on the response of the renin-angiotensin system and serum potassium to nebulized salbutamol was investigated in a randomized, double-blind, crossover study in eight healthy volunteers using a factorial block design. On study days, subjects received lisinopril 20 mg orally or identical placebo tablets followed 3 h later by nebulized salbutamol or placebo inhalation; plasma renin, angiotensin II, serum angiotensin-converting enzyme and potassium were measured at intervals for 120 min after inhalation. 3. Following salbutamol, plasma renin and angiotensin II concentrations were increased significantly compared with placebo [mean (SEM) plasma renin of 61.7 (15.6) mu-units/ml and angiotensin II of 17.7 (5.4) pg/mol 15 min after salbutamol, P < 0.05 versus placebo]. Baseline plasma renin concentrations were increased [160.1 (20.6) mu-units/ml] and baseline plasma angiotensin II concentrations were reduced [1.4 (0.1) pg/ml] by lisinopril, P < 0.05 versus placebo in each case. Inhibition of angiotensin-converting enzyme completely inhibited this salbutamol-induced rise in plasma angiotensin II [mean (SEM) plasma angiotensin II of 1.5 (0.4) pg/ml 15 min after salbutamol, P < 0.05 versus placebo] but had no effect on the changes in plasma renin concentrations after the beta 2-agonist [mean (SEM) plasma renin of 198.4 (18.9) mu-units/ml 15 min after salbutamol].(ABSTRACT TRUNCATED AT 250 WORDS)
Millar
E A
EA
Department of Respiratory Medicine, Western Infirmary, Glasgow, U.K.
McInnes
G T
GT
Thomson
N C
NC
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011188:Potassium / Q000097:blood*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000804:Angiotensin II; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D000420:Albuterol; D011188:Potassium