Pharmacological characterization of endothelin-induced rat pulmonary arterial dilatation

1 The aim of study was to characterize endothelin (ET)-induced vasodilatation in isolated extrapulmonary rat arteries (EPA)d and in intrapulmonary arteries (IPA) preconstricted with 1 mu M phenylephrine. 2 The ET-3 (1 nM - 100 nM)- and ET-1 (10 nM - 100 nM)-induced transient vasodilatations in EPA were more potent than those in IPA. The vasodilatation induced by ET-3 (100 nM) was larger than that induced by ET-1 (100 nM). 3 Both the ETB antagonist, BQ788 (3 mu M) and or endothelium denudation but not the ETA antagonist, BQ123 (3 mu M), abolished the vasodilatation induced by ET-1 or ET-3 (100 nM each) in EPA and in IPA. The ATP-sensitive K+channel blocker, glibenclamide (20 mu M) and the nitric oxide synthase inhibitor, N-G-monomethyl-L-arginine (L-NMMA, 1 mM) suppressed the ET-induced vasodilatation in EPA and in IPA. 4 We conclude that the vasodilatation induced by endothelins is markedly reduced in rat isolated IPA, and suggest that the endothelial ETB-mediated vasodilatation varies depending on rat pulmonary arterial regions. Furthermore, ETB-mediated vasodilatation involves activation of ATP-sensitive K+ channels and of nitric oxide synthase in rat isolated EPA and IPA.