Pharmacological characterization of endothelin-induced rat pulmonary arterial dilatation

Abstract

1. The aim of study was to characterize endothelin (ET)-induced vasodilatation in isolated extrapulmonary rat arteries (EPA) and in intrapulmonary arteries (IPA) preconstricted with 1 μM 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 ET(B) antagonist, BQ788 (3 μM) and or endothelium denudation, but not the ETA antagonist, BQ123 (3 μM), 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 μM) 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 ET(B)-mediated vasodilatation varies depending on rat pulmonary arterial regions. Furthermore, ET(B)-mediated vasodilatation involves activation of ATP-sensitive K+ channels and of nitric oxide synthase in rat isolated EPA and IPA.