Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

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dc.contributor.authorLameu, Claudiana
dc.contributor.authorPontieri, Vera
dc.contributor.authorGuerreiro, Juliano R.
dc.contributor.authorOliveira, Eduardo F. [UNIFESP]
dc.contributor.authorSilva, Carlos Alberto da
dc.contributor.authorGiglio, Joyce M.
dc.contributor.authorMelo, Robson L.
dc.contributor.authorCampos, Ruy Ribeiro [UNIFESP]
dc.contributor.authorMartins de Camargo, Antonio Carlos
dc.contributor.authorUlrich, Henning
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionInst Butantan
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed FABC
dc.date.accessioned2016-01-24T14:05:42Z
dc.date.available2016-01-24T14:05:42Z
dc.date.issued2010-12-01
dc.description.abstractBaroreflex sensitivity is disturbed in many people with cardiovascular diseases such as hypertension. Brain deficiency of nitric oxide (NO), which is synthesized by NO synthase (NOS) in the citrulline-NO cycle (with argininosuccinate synthase (ASS) activity being the rate-limiting step), contributes to impaired baroreflex. We recently showed that a decapeptide isolated from Bothrops jararaca snake venom, denoted Bj-PRO-10c, exerts powerful and sustained antihypertensive activity. Bj-PRO-10c promoted vasodilatation dependent on the positive modulation of ASS activity and NO production in the endothelium, and also acted on the central nervous system, inducing the release of GABA and glutamate, two important neurotransmitters in the regulation of autonomic systems. We evaluated baroreflex function using the regression line obtained by the best-fit points of measured heart rate (HR) and mean arterial pressure (MAP) data from spontaneously hypertensive rats (SHRs) treated with Bj-PRO-10c. We also investigated molecular mechanisms involved in this effect, both in vitro and in vivo. Bj-PRO-10c mediated an increase in baroreflex sensitivity and a decrease in MAP and HR. the effects exerted by the peptide include an increase in the gene expression of endothelial NOS and ASS. Bj-PRO-10c-induced NO production depended on intracellular calcium fluxes and the activation of a G(i/o)-protein-coupled metabotropic receptor. Bj-PRO-10c induced NO production and the gene expression of ASS and endothelial NOS in the brains of SHRs, thereby improving baroreflex sensitivity. Bj-PRO-10c may reveal novel approaches for treating diseases with impaired baroreflex function. Hypertension Research (2010) 33, 1283-1288; doi: 10.1038/hr.2010.208en
dc.description.affiliationUniv São Paulo, Dept Bioquim, Inst Quim, BR-05508900 São Paulo, Brazil
dc.description.affiliationInst Butantan, CAT, CEPID, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, ESALQ, Lab Bioquim Peptideos & Prot, Dept Ciencias Biol, BR-09500900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliationUniv Fed FABC, Nat & Human Sci Ctr, Santo Andre, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Dept Cell Biol & Dev, BR-05508900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent1283-1288
dc.identifierhttp://dx.doi.org/10.1038/hr.2010.208
dc.identifier.citationHypertension Research. London: Nature Publishing Group, v. 33, n. 12, p. 1283-1288, 2010.
dc.identifier.doi10.1038/hr.2010.208
dc.identifier.issn0916-9636
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33090
dc.identifier.wosWOS:000285087000011
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofHypertension Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectargininosuccinate synthaseen
dc.subjectbaroreflex sensitivityen
dc.subjectBothrops jararaca venomen
dc.subjectnitric oxideen
dc.subjectproline-rich oligopeptideen
dc.titleBrain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive ratsen
dc.typeinfo:eu-repo/semantics/article
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