To gain more insight into the complex pulmonary interactions of endothelins (ET), we studied airway and vascular responses to endothelins in isolated perfused @entity35 lungs in the presence of the novel ET(B)-receptor antagonist @entity11345 . In particular we focused on airway responses and on @entity4770 release. The effectiveness of @entity11345 in our system was shown by its ability to concentration-dependently prevent vasoconstriction (IC50 0.1 microM), bronchoconstriction (IC50 0.1 microM) and @entity4770 production (IC50 < 0.1 microM) induced by the ET(B)-receptor agonist @entity13071 (1 nmol). Airway responses to @entity1827 : @entity1827 -induced bronchoconstriction was aggravated by @entity11344 (1 or 8 microM), while @entity11345 pretreatment (1 or 8 microM) showed no significant effect. Simultaneous treatment with 8 microM @entity11344 and @entity11345 attenuated the @entity1827 -induced bronchoconstriction. Vascular responses to @entity1827 : @entity1827 (1 nmol)-induced vasoconstriction was potentiated by @entity11345 (1 or 8 microM), but attenuated by the ET(A)-receptor antagonist @entity11344 (1 microM). In the presence of @entity11345 diminished amounts of the stable @entity4770 metabolite @entity9077 were detected in the perfusate. Simultaneous treatment with 8 microM @entity11344 and @entity11345 completely prevented the @entity1827 -induced vasoconstriction. CONCLUSIONS: Both ET(A)- and ET(B)-receptors contribute to @entity1827 -induced vasoconstriction and bronchoconstriction. The @entity1827 -induced vasoconstriction is attenuated by stimulation of ET(B)-receptors, a response that is partly mediated by @entity4770 . Due to the mutual interactions between ET(A)- and ET(B)-receptors, simultaneous inhibition of both receptors is required to prevent the deleterious effects of @entity1827 on lung functions.

The interaction of endothelin receptor responses in the isolated perfused XXXX lung.

@entity11345 :: ('MESH:C086539', 'Chemical') :: ['BQ788'] @entity4770 :: ('MESH:D011464', 'Chemical') :: ['prostacyclin'] @entity9077 :: ('MESH:D015121', 'Chemical') :: ['6-keto-PGF1alpha'] @entity1827 :: ('24323(Tax:10116)', 'Gene') :: ['ET-1'] @entity11344 :: ('MESH:C072247', 'Chemical') :: ['BQ123'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity13071 :: ('MESH:C074308', 'Chemical') :: ['IRL1620']
@entity35 :: (10116,Species) :: ['rat']
