Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial hyperresponsiveness to methacholine in patients with bronchial asthma

It is unclear whether angiotensin II receptors are involved in bronchial hy perresponsiveness in asthmatic patients. We examined the effect of losartan , a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in eight patients with stable asthma . Bronchial responsiveness to methacholine, assessed as the concentration o f methacholine producing a 20% fall in FEV1 (PC20-FEV1) and a 35% fall in s tandardized partial expiratory flow at 40% of FVC (PC35-PEF40), was measure d on two occasions 2 wk apart. Losartan (50 mg once a day) or a placebo was orally administered for 1 wk before methacholine provocation test in a dou ble-blind, randomized, crossover fashion. Although the PC20-FEV1 values aft er placebo (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/m l) and losartan (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC35-PEF40 values significantly (p = 0.034) increased from 0.258 (GSEM, 0.156) mg/ml with placebo to 0.456 (GSEM, 0.186) mg/ml with lo sartan. We conclude that AT1 receptors are involved in bronchial hyperrespo nsiveness in asthmatic patients. This is the first report demonstrating the involvement of AT1 receptors in bronchial asthma.