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

Abstract

It is unclear whether angiotensin II receptors are involved in bronchial hyperresponsiveness 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 of methacholine producing a 20% fall in FEV(1) (PC(20)-FEV(1)) and a 35% fall in standardized partial expiratory flow at 40% of FVC (PC(35)-PEF(40)), was measured 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 double-blind, randomized, crossover fashion. Although the PC(20)-FEV(1) values after placebo (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/ml) and losartan (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC(35)-PEF(40) 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 losartan. We conclude that AT1 receptors are involved in bronchial hyperresponsiveness in asthmatic patients. This is the first report demonstrating the involvement of AT1 receptors in bronchial asthma.