Pharmacological evaluation of R(+)-pulegone on cardiac excitability: Role of potassium current blockage and control of action potential waveform

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dc.contributor.authorSantos-Miranda, Artur
dc.contributor.authorGondim, Antonio Nei
dc.contributor.authorRodrigues Menezes-Filho, Jose Evaldo
dc.contributor.authorLins Vasconcelos, Carla Marina
dc.contributor.authorCruz, Jader Santos
dc.contributor.authorRoman-Campos, Danilo [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniv Estado Bahia
dc.contributor.institutionUniv Fed Sergipe
dc.date.accessioned2016-01-24T14:37:49Z
dc.date.available2016-01-24T14:37:49Z
dc.date.issued2014-09-01
dc.description.abstractIntroduction: R(+)-pulegone is a ketone monoterpene and it is the main constituent of essential oils in several plants. Previous studies provided some evidence that R(+)-pulegone may act on isolated cardiac myocytes. in this study, we evaluated in extended detail, the pharmacological effects of R(+)-pulegone on cardiac tissue.Methods: Using in vivo measurements of rat cardiac electrocardiogram (ECG) and patch-clamp technique in isolated myocytes we determinate the influence of R(+)-pulegone on cardiac excitability.Results: R(+)-pulegone delayed action potential repolarization (APR) in a concentration-dependent manner (EC50 = 775.7 +/- 1.48, 325.0 +/- 1.30, 469.3 +/- 1.91 mu M at 10, 50 and 90% of APR respectively). in line with prolongation of APR R(+)-pulegone, in a concentration-dependent manner, blocked distinct potassium current components (transient outward potassium current (I-to), rapid delayed rectifier potassium current (I-kr), inactivating steady state potassium current (I-ss) and inward rectifier potassium current (I-K1)) (EC50 = 1441 +/- 1.04; 605.0 +/- 1.22, 818.7 +/- 1.22; 1753 +/- 1.09 mu M for I-to, I-Kr, I-ss and I-K1, respectively). the inhibition occurred in a fast and reversible way, without changing the steady-state activation curve, but instead shifting to the left the steady-state inactivation curve (V-1/2 from -56.92 +/- 0.35 to 67.52 +/- 0.19 mV). in vivo infusion of 100 mg/kg R(+)-pulegone prolonged the QTc (similar to 40%) and PR (similar to 62%) interval along with reducing the heart rate by similar to 26%.Conclusion: Taken together, R(+)-pulegone prolongs the APR by inhibiting several cardiomyocyte current components in a concentration-dependent manner. This occurs through a direct block by R(+)pulegone of the channel pore, followed by a left shift on the steady state inactivation curve. Finally, R(+)-pulegone induced changes in some aspects of the ECG profile, which are in agreement with its effects on potassium channels of isolated cardiomyocytes. (C) 2014 Elsevier GmbH. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Estado Bahia, Dept Educ, Lab Lab Biofis & Farmacol Coracao, Guanambi, Bahia, Brazil
dc.description.affiliationUniv Fed Sergipe, Dept Fisiol, Lab Biofis Coracao, Aracaju, Sergipe, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFAPITEC/SE
dc.format.extent1146-1153
dc.identifierhttp://dx.doi.org/10.1016/j.phymed.2014.05.007
dc.identifier.citationPhytomedicine. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 21, n. 10, p. 1146-1153, 2014.
dc.identifier.doi10.1016/j.phymed.2014.05.007
dc.identifier.issn0944-7113
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38175
dc.identifier.wosWOS:000340336700003
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofPhytomedicine
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectPulegoneen
dc.subjectMyocyteen
dc.subjectHearten
dc.subjectElectrocardiogramen
dc.subjectAction potentialen
dc.subjectPotassium currenten
dc.titlePharmacological evaluation of R(+)-pulegone on cardiac excitability: Role of potassium current blockage and control of action potential waveformen
dc.typeinfo:eu-repo/semantics/article
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