Pharmacological characterization of endothelin-induced rat pulmonary arterial dilatation |
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Authors: | Tooru Higashi Takeshi Ishizaki Kazuo Shigemori Takaki Yamamura Tuguhiko Nakai |
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Institution: | Third Department of Internal Medicine, Fukui Medical School, 23-3 Matuoka-chou, Yoshida-gun, Fukui, 910-11, Japan;*International Research Laboratories, Ciba-Geigy Japan, Takarazuka 665, Japan |
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Abstract: | - 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.
- 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).
- Both the ETB 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, NG-monomethyl-L-arginine (L-NMMA, 1 mM) suppressed the ET-induced vasodilatation in EPA and in IPA.
- 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.
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Keywords: | Endothelin-1 endothelin-3 vasodilatation BQ788 BQ123 nitric oxide synthase ATP-sensitive K+ channel ETB receptor intrapulmonary artery extrapulmonary artery |
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