Hydrocortisone abolishes the angiotensin II-mediated potentiation of endothelin-I in bovine bronchi

Angiotensin II potentiates methacholine-evoked bronchoconstriction both in bovine airways in vitro and in asthmatic patients in vivo. Angiotensin II a lso potentiates endothelin-1-evoked contractions in vitro, but fails to alt er such contractions in vivo. One possible confounding factor in patients i s their use of inhaled corticosteroids. Accordingly the present study exami ned the effects of hydrocortisone (cortisol) on contractions evoked by meth acholine and endothelin-1 in the presence and absence of angiotensin II. Co ntractions of rings of isolated bovine airways were measured isometrically in organ baths. Concentration-response curves were obtained for endothelin- 1 or methacholine in the presence and absence of angiotensin II, hydrocorti sone and a combination of angiotensin II and hydrocortisone. Hydrocortisone abolished the angiotensin II-mediated potentiation of endothelin-1-evoked, but not methacholine-evoked, contractions. Hydrocortisone alone evoked the enhancement of methacholine responses, similar to the effect produced by a ngiotensin II. While species differences may exist, our present results sug gest that the use of corticosteroids can have a profound effect on the inte raction between angiotensin II and endothelin-1. Accordingly, the presence of inhaled corticosteroids might explain the differences between the result s obtained in vitro and in vivo.