Effect of candesartan, a type 1 angiotensin II receptor antagonist, on bronchial hyper-responsiveness to methacholine in patients with bronchial asthma.
OBJECTIVE
Angiotensin II is a putative mediator in bronchial asthma. There have been very few studies investigating the involvement of angiotensin II receptors in bronchial hyper-responsiveness in asthmatic patients. We examined the effect of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in patients with asthma.


METHODS
Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV1 (PC20-FEV1), was measured on three occasions 2 weeks apart in 11 stable asthmatic patients. Candesartan cilexetil (8 mg once a day) or a placebo was orally administered for 1 week before the methacholine provocation test in a double-blind, randomized, crossover manner.


RESULTS
Although there were no significant differences between treatment periods in FEV1 values at baseline, the geometric mean (95% CI) PC20-FEV1 values increased significantly (P = 0.041) from 0.691 (0.379, 1.259) mg ml-1 with placebo to 0.837 (0.506, 1.384) mg ml-1 with candesartan. Candesartan decreased the mean (95% CI) arterial blood pressure (placebo: 95.6 (89.0, 102.2) mmHg, candesartan: 86.4 (79.8, 93.1) mmHg, P = 0.015). There was no correlation between the change in blood pressure and the change in PC20-FEV1.


CONCLUSIONS
We conclude that AT1 receptors are involved in bronchial hyper-responsiveness in asthmatic patients.
Myou
Shigeharu
S
The Third Department of Internal Medicine, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan. myous@nifty.com
Fujimura
Masaki
M
Kamio
Yumie
Y
Kita
Toshiyuki
T
Watanabe
Kazuyoshi
K
Ishiura
Yoshihisa
Y
Hashimoto
Takuma
T
Nakao
Shinji
S
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001980:Bronchi / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage*; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016085:Bronchoconstrictor Agents; D013777:Tetrazoles; D016210:Methacholine Chloride; D000804:Angiotensin II; C081643:candesartan