title: Angiotensin II potentiates methacholine-induced bronchoconstriction in human airway both in vitro and in vivo.
abstract: Angiotensin II levels are elevated in patients with acute severe asthma. In addition, intravenous angiotensin II causes bronchoconstriction in mild asthmatic patients. In the present study, we examined the effects of this hormone on bronchi in vitro and its interaction with the cholinergic agonist methacholine both in vivo and in vitro. Contractions of rings of human bronchi were measured isometrically. Concentration-response curves were obtained to angiotensin II and to methacholine in the presence and absence of angiotensin II. In addition, seven asthmatic patients with mild bronchial hyperreactivity to methacholine received placebo, angiotensin II, 1 or 2 ng.kg-1.min, by infusion, followed by methacholine challenge. Forced expiratory volume in one second (FEV1) values were measured at baseline, at the end of the infusion and during methacholine challenge. Angiotensin II alone in vitro evoked small contractions of human bronchi ( < 0.25 g wt). Pre-incubation with low concentrations of angiotensin II significantly enhanced contractions to methacholine. In mild asthmatic patients, angiotensin II alone evoked no change in baseline FEV1 values at the levels studied. Compared to placebo, angiotensin II 2 ng.kg-1.min, but not 1 ng.kg-1.min, evoked a significant increase in bronchial reactivity to methacholine. Angiotensin II in subthreshold concentrations enhances methacholine-evoked bronchoconstrictions both in human in vitro and in mild asthmatic patients in vivo. Our findings suggest a novel role for angiotensin II as a putative mediator in asthma.
authors.affiliation: Dept of Respiratory Medicine, Western Infirmary, University of Glasgow, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Millar
authors.forename: J E
authors.initials: JE
authors.lastname: Nally
authors.forename: N C
authors.initials: NC
authors.lastname: Thomson
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D013268:Stimulation, Chemical
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D000804:Angiotensin II