Inhaled loop diuretics and basal airway responsiveness in man: evidence of a role for cyclo-oxygenase products.
Inhaled frusemide protects asthmatic airways against a wide variety of bronchoconstrictor stimuli by unknown mechanisms. To investigate whether inhaled loop diuretics modulate baseline bronchial responsiveness, a randomized, double-blind, placebo-controlled study was conducted to test the ability of frusemide (40 mg) and bumetanide (2 mg) to displace concentration-response curves with methacholine in 14 healthy volunteers. In addition, separate randomized, double-blind studies were carried out to evaluate the effects of oral flurbiprofen, a potent cyclo-oxygenase inhibitor, on the protective action of frusemide against methacholine-induced bronchoconstriction. Inhaled loop diuretics significantly increased the provocative concentration of methacholine causing a 15% decrease in forced expiratory volume in one second (PC15FEV1) from the geometric mean (range) value of 58.6 (9.2-233) mg.ml-1 after placebo administration, to 129 (13.8-505) and to 106 (6.6-510) mg.ml-1 after administration of frusemide and bumetanide, respectively. Similar results were obtained when data from partial flow-volume curves were used for analysis. In the eight subjects studied, pretreatment with oral placebo and inhaled frusemide reduced airway responsiveness to methacholine, with a geometric mean (range) PC15FEV1 value of 116 (25.4-405) mg.ml-1, and premedication with oral flurbiprofen abolished this protective effect, the geometric mean (range) PC15FEV1 methacholine being reduced to a value of 50.3 (16.6-189) mg.ml-1. In addition, oral flurbiprofen alone failed to alter airway responsiveness to methacholine. In view of these findings, it is suggested that bronchoprotective prostaglandins may mediate the effects of loop diuretics against methacholine-induced bronchoconstriction in man.
Polosa
R
R
Istituto Malattie Apparato Respiratorio, Università di Catania, Italy.
Rajakulasingam
K
K
Prosperini
G
G
Magrì
S
S
Mastruzzo
C
C
Holgate
S T
ST
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D002034:Bumetanide / Q000008:administration & dosage* / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000494:pharmacology; D005541:Forced Expiratory Volume / Q000187:drug effects; D005665:Furosemide / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D011453:Prostaglandins / Q000502:physiology*
D000336:Aerosols; D011453:Prostaglandins; D016210:Methacholine Chloride; D002034:Bumetanide; D005480:Flurbiprofen; D005665:Furosemide