ANGIOTENSIN-II ENHANCES RESPONSES TO ENDOTHELIN-1 IN BOVINE BRONCHIALSMOOTH-MUSCLE

Angiotensin II and endothelin-1 are putative mediators in asthma. In t his study we have examined the effect of angiotensin II on endothelin- 1-induced contractions in bovine bronchi and the receptor types involv ed in the response to these agonists. Angiotensin II alone is very low in potency, producing only small contractions. In the presence of ang iotensin II. 10(-7) or 3 x 10(-7) M, contractions evoked by endothelin -1 were markedly enhanced. The AII(1)-receptor antagonist, losartan, a bolished this enhancement suggesting that angiotensin II exerts this e ffect via an AII(1)-receptor. The contraction evoked by endothelin-1 i s mediated via an EtA(B)-receptor subtype since the Et(A)-receptor ant agonist FR139317 attenuated the response. This is offset by an inhibit ory Et(B)-type receptor, resulting in a larger contraction when these receptors ape desensitized. Indeed, the Et(B)-receptor agonist sarafot oxin S6c reversed methacholine-evoked tone in a concentration-dependen t manner In conclusion, angiotensin II potentiates contractions evoked by endothelin-1 in bovine bronchi. This may be a mechanism by which a ngiotensin II-which has little activity in bronchi-may evoke substanti al changes in;airway tone. Angiotensin II evokes this potentiation via AII(1)-receptors, whilst endothelin-1 evokes contraction via Et(A)-re ceptors, an action which is offset by an inhibitory effect of Et(B)-re ceptors.