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.author Lameu, Claudiana
dc.contributor.author Pontieri, Vera
dc.contributor.author Guerreiro, Juliano R.
dc.contributor.author Oliveira, Eduardo F. [UNIFESP]
dc.contributor.author Silva, Carlos Alberto da
dc.contributor.author Giglio, Joyce M.
dc.contributor.author Melo, Robson L.
dc.contributor.author Campos, Ruy Ribeiro [UNIFESP]
dc.contributor.author Martins de Camargo, Antonio Carlos
dc.contributor.author Ulrich, Henning
dc.date.accessioned 2016-01-24T14:05:42Z
dc.date.available 2016-01-24T14:05:42Z
dc.date.issued 2010-12-01
dc.identifier http://dx.doi.org/10.1038/hr.2010.208
dc.identifier.citation Hypertension Research. London: Nature Publishing Group, v. 33, n. 12, p. 1283-1288, 2010.
dc.identifier.issn 0916-9636
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/33090
dc.description.abstract Baroreflex 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.2010.208 en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 1283-1288
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Hypertension Research
dc.rights Acesso aberto
dc.subject argininosuccinate synthase en
dc.subject baroreflex sensitivity en
dc.subject Bothrops jararaca venom en
dc.subject nitric oxide en
dc.subject proline-rich oligopeptide en
dc.title Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats en
dc.type Artigo
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Inst Butantan
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Univ Fed FABC
dc.description.affiliation Univ São Paulo, Dept Bioquim, Inst Quim, BR-05508900 São Paulo, Brazil
dc.description.affiliation Inst Butantan, CAT, CEPID, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, ESALQ, Lab Bioquim Peptideos & Prot, Dept Ciencias Biol, BR-09500900 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliation Univ Fed FABC, Nat & Human Sci Ctr, Santo Andre, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Dept Cell Biol & Dev, BR-05508900 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Bioquim, São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil
dc.identifier.doi 10.1038/hr.2010.208
dc.description.source Web of Science
dc.identifier.wos WOS:000285087000011



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