The semi-synthetic kaurane ent-16 alpha-methoxykauran-19-oic acid induces vascular relaxation and hypotension in rats

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dc.contributor.authorHipolito, Ulisses V.
dc.contributor.authorRocha, Juliana T.
dc.contributor.authorPalazzin, Nathalia B.
dc.contributor.authorRodrigues, Gerson Jhonatan [UNESP]
dc.contributor.authorCrestani, Carlos Cesar [UNESP]
dc.contributor.authorCorrea, Fernando M.
dc.contributor.authorBonaventura, Daniella
dc.contributor.authorAmbrosio, Sergio R.
dc.contributor.authorBendhack, Lusiane M.
dc.contributor.authorResstel, Leonardo B.
dc.contributor.authorTirapelli, Carlos R.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniv Franca
dc.date.accessioned2014-05-20T13:25:36Z
dc.date.available2014-05-20T13:25:36Z
dc.date.issued2011-06-25
dc.description.abstractThe present work investigates the mechanisms involved in the vasorelaxant effect of ent-16 alpha-methoxykauran-19-oic acid (KA-OCH(3)), a semi-synthetic derivative obtained from the kaurane-type diterpene ent-kaur-16-en-19-oic acid (kaurenoic acid). Vascular reactivity experiments were performed in aortic rings isolated from male Wistar rats using standard muscle bath procedures. The cytosolic calcium concentration ([Ca(2+)]c) was measured by confocal microscopy using the fluorescent probe Fluo-3 AM. Blood pressure measurements were performed in conscious rats. KA-OCH(3) (10,50 and 100 mu mol/l) inhibited phenylephrine-induced contraction in either endothelium-intact or endothelium-denuded rat aortic rings. KA-OCH(3) also reduced CaCl(2)-induced contraction in a Ca(2+)-free solution containing KCl (30 mmol/l) or phenylephrine (0.1 mu mol/l). KA-OCH(3) (0.1-300 mu mol/l) concentration-dependently relaxed endothelium-intact and endothelium-denuded aortas pre-contracted with either phenylephrine or KCl, to a greater extent than kaurenoic acid. Moreover, a Ca(2+) mobilisation study showed that KA-OCH(3) (100 mu mol/l) inhibited the increase in Ca(2+) concentration in smooth muscle and endothelial cells induced by phenylephrine or KCl. Pre-incubation of intact or denuded aortic rings with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mu mol/l), 7-nitroindazole (100 mu mol/l), wortmannin (0.5 mu mol/l) and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ 1 mu mol/l) produced a rightward displacement of the KA-OCH(3) concentration-response curve. Intravenous administration of KA-OCH(3) (1-10 mg/kg) reduced mean arterial blood pressure in normotensive rats. Collectively, our results show that KA-OCH(3) induces vascular relaxation and hypotension. The mechanisms underlying the cardiovascular actions of KA-OCH(3) involve blockade of Ca(2+) influx and activation of the NO-cGMP pathway. (C) 2011 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv São Paulo, Escola Enfermagem Ribeirao Preto, Coll Nursing Ribeirao Preto, Dept Psychiat Nursing & Human Sci,Lab Pharmacol, BR-14040902 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniv São Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, BR-14040902 Ribeirao Preto, SP, Brazil
dc.description.affiliationSão Paulo State Univ, UNESP, Sch Pharmaceut Sci, Dept Nat Act Principles & Toxicol, Araraquara, SP, Brazil
dc.description.affiliationUniversidade Federal de Minas Gerais (UFMG), Inst Biol Sci, Dept Pharmacol, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Franca, Franca, SP, Brazil
dc.description.affiliationUniv São Paulo, Fac Pharmaceut Sci Ribeirao Preto, Pharmacol Lab, Dept Chem & Phys, BR-14040902 Ribeirao Preto, SP, Brazil
dc.description.affiliationUnespSão Paulo State Univ, UNESP, Sch Pharmaceut Sci, Dept Nat Act Principles & Toxicol, Araraquara, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 09/52629-4
dc.format.extent402-410
dc.identifierhttp://dx.doi.org/10.1016/j.ejphar.2011.04.019
dc.identifier.citationEuropean Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 660, n. 2-3, p. 402-410, 2011.
dc.identifier.doi10.1016/j.ejphar.2011.04.019
dc.identifier.fileWOS000291623600023.pdf
dc.identifier.issn0014-2999
dc.identifier.lattes1117432571971568
dc.identifier.urihttp://hdl.handle.net/11449/8132
dc.identifier.wosWOS:000291623600023
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Pharmacology
dc.relation.ispartofjcr3.040
dc.relation.ispartofsjr1,057
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.subjectent-16 alpha-methoxykauran-19-oic aciden
dc.subjectRelaxationen
dc.subjectRat aortaen
dc.subjectDiterpeneen
dc.subjectCa(2+)en
dc.titleThe semi-synthetic kaurane ent-16 alpha-methoxykauran-19-oic acid induces vascular relaxation and hypotension in ratsen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.author.lattes1117432571971568[5]
unesp.author.orcid0000-0002-1942-858X[5]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt
unesp.departmentPrincípios Ativos Naturais e Toxicologia - FCFpt

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Araraquara - FCF - Faculdade de Ciências Farmacêuticas