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Analysis of the mechanisms underlying the vasorelaxant action of kaurenoic acid in the isolated rat aorta.

Abstract：

:The present work describes the mechanisms involved in the vasorelaxant effect of the diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid). Kaurenoic acid (10, 50 and 100 microM) concentration-dependently inhibited phenylephrine and KCl-induced contraction in either endothelium-intact or -denuded rat aortic rings. Kaurenoic acid also reduced CaCl(2)-induced contraction in Ca(2+)-free solution containing KCl (30 mM). The diterpene did not interfere with Ca(2+) release from intracellular stores mediated by either phenylephrine (1 microM) or caffeine (30 mM). Kaurenoic acid (1-450 microM) concentration dependently relaxed phenylephrine-pre-contracted rings with intact (72.27+/-3.79%) or denuded endothelium (73.28+/-5.91%). The diterpene also relaxed KCl-pre-contracted rings with intact (80.44+/-3.68%) or denuded endothelium (78.12+/-1.26%). Pre-incubation of denuded aortic rings with N(G)-nitro-l-arginine methyl ester (l-NAME, 100 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM) and 7-nitroindazole (100 microM) reduced kaurenoic acid-induced relaxation (percentage of relaxation: 49.12+/-3.26%, 53.10+/-6.72% and 51.74+/-4.76%, respectively). Indomethacin (10 microM) did not affect kaurenoic acid-induced relaxation. In endothelium-intact rings, 7-nitroindazole and N(pi)-nitro-l-arginine (l-NNA, 100 microM) displaced the curves for the diterpene to the right. Tetraethylammonium (5 mM), 4-amynopiridine (1 mM) and charybdotoxin (0.1 microM) caused a rightward displacement of the concentration-response curve for kaurenoic acid. Conversely, neither apamin (1 microM) nor glibenclamide (3 microM) affected kaurenoic acid-induced relaxation. Collectively, our results provide functional evidence that the effects elicited by kaurenoic acid involve extracellular Ca(2+) influx blocked. Its effects are also partly mediated by the activation of NO-cGMP pathway and the opening of K(+) channels sensitive to charybdotoxin and 4-amynopiridine. Additionally, the activation of the endothelial and neuronal NO synthase isoforms are required for the relaxant effect induced by kaurenoic acid.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Tirapelli CR,Ambrosio SR,da Costa FB,Coutinho ST,de Oliveira DC,de Oliveira AM

doi

10.1016/j.ejphar.2004.04.003

keywords:

subject

Has Abstract

pub_date

2004-05-25 00:00:00

pages

233-41

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014299904003784

journal_volume

492

pub_type

杂志文章

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