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. Angi otensin II causes bronchoconstriction in mild asthmatics and potentiat es methacholine-evoked bronchoconstriction both in vitro and in vivo. To evaluate the effect of angiotensin II on histamine-induced bronchoc onstriction, human bronchial rings (n=6) were obtained from lung tissu e at thoracotomy and were prepared in organ baths. Contractions were m easured isometrically and cumulative concentration-response curves obt ained to angiotensin II alone and to histamine in the presence and abs ence of threshold concentrations of angiotensin II. Eight asthmatic pa tients with bronchial hyper-reactivity to histamine were challenged wi th 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. FEV1 was measured prior to, dur ing the infusion and during the histamine challenge. Angiotensin II (3 x 10(-7) M and 10(-6) M) alone evoked small contractions (<0.25 g) of human bronchi in vitro, but pre-incubation with threshold concentrati ons of angiotensin II (10(-7) M, 3 x 10(-7) M and 10(-6) M) had no eff ect on histamine-evoked contractions, In asthmatic patients, angiotens in II alone had no effect on baseline FEV1 at the low levels infused a nd did not affect the response to nebulized histamine as measured by t he PC20 histamine: Geometric mean (range) PC20 histamine (mg ml(-1)) s creening day 3.58 (1.26-7.75), placebo infusion 2.67 (0.89-9.57), angi otensin II 1 ng kg(-1) min(-1) 2.45 (0.42-6.97) and angiotensin II 2 n g kg(-1) min(-1) 3.09 (0.88-10.78). It is concluded that, in contrast to its potentiating effect on methacholine-induced bronchoconstriction , angiotensin II has no effect on histamine-evoked bronchoconstriction in human bronchi in vitro or in vivo.