Pharmacological characterization of endothelin‐induced rat pulmonary arterial dilatation

Article date: June 1997

By: Tooru Higashi, Takeshi Ishizaki, Kazuo Shigemori, Takaki Yamamura, Tuguhiko Nakai, in Volume 121, Issue 4, pages 782-786

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.

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.

British Journal of Pharmacology (1997) 121, 782–786; doi:10.1038/sj.bjp.0701177

DOI: 10.1038/sj.bjp.0701177

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