ANGIOTENSIN-II POTENTIATES METHACHOLINE-INDUCED BRONCHOCONSTRICTION IN HUMAN AIRWAY BOTH IN-VITRO AND IN-VIVO

Angiotensin II levels are elevated in patients with acute severe asthm a. In addition, intravenous angiotensin II causes bronchoconstriction in mild asthmatic patients, In the present study, we examined the effe cts of this hormone on bronchi in vitro and its interaction with the c holinergic agonist methacholine both in vivo and in vitro. Contraction s of rings of human bronchi were measured isometrically, Concentration -response curves were obtained to angiotensin II and to methacholine i n the presence and absence of angiotensin II, In addition, seven asthm atic patients with mild bronchial hyperreactivity to methacholine rece ived placebo, angiotensin II, 1 or 2 ng . kg(-1) min, by infusion, fol lowed by methacholine challenge. Forced expiratory volume in one secon d (FEV(1)) values were measured at baseline, at the end of the infusio n and during methacholine challenge. Angiotensin II alone in vitro evo ked small contractions of human bronchi (<0.25 g wt), Pre-incubation w ith low concentrations of angiotensin If significantly enhanced contra ctions to methacholine, In mild asthmatic patients, angiotensin II alo ne evoked no change in baseline FEV1 values at the levels studied, Com pared to placebo, angiotensin II 2 ng . kg(-1). min, but not 1 ng . kg (-1). min, evoked a significant increase in bronchial reactivity to me thacholine. Angiotensin II in subthreshold concentrations enhances met hacholine-evoked bronchoconstrictions both in human bronchi in vitro a nd in mild asthmatic patients in vivo, Our findings suggest a novel ro le for angiotensin II as a putative mediator in asthma.