Effect of angiotensin II on histamine-induced bronchoconstriction in the human airway both in vitro and in vivo

The renin-angiotensin system is activated in acute severe asthma. Angiotensin II causes bronchoconstriction in mild asthmatics and potentiates methacholine-evoked bronchoconstriction both in vitro and in vivo. To evaluate the effect of angiotensin II on histamine-induced bronchoconstriction, human bronchial rings ( n=6) were obtained from lung tissue at thoracotomy and were prepared in organ baths. Contractions were measured isometrically and cumulative concentration-response curves obtained to angiotensin II alone and to histamine in the presence and absence of threshold concentrations of angiotensin II. Eight asthmatic patients with bronchial hyper-reactivity to histamine were challenged with histamine during intravenous infusion of placebo, angiotensin II 1 ng kg −1 min −1 and angiotensin II 2 ng kg −1 min −1 administered in a randomized, double-blind fashion. FEV 1 was measured prior to, during the infusion and during the histamine challenge. Angiotensin II (3 × 10 −7 m and 10 −6 m) alone evoked small contractions (