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Reversing gene expression in cardiovascular target organs following chronic depression of the paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in spontaneous hypertensive rats

dc.contributor.authorGeraldes, Vera
dc.contributor.authorGonçalves-Rosa, Nataniel
dc.contributor.authorTavares, Cristiano
dc.contributor.authorPaton, Julian F.R.
dc.contributor.authorRocha, Isabel
dc.date.accessioned2020-07-22T09:35:59Z
dc.date.available2020-07-22T09:35:59Z
dc.date.issued2016
dc.description© 2016 Elsevier B.V. All rights reserved.pt_PT
dc.description.abstractBackground: Chronic overexpression of an inwardly rectifying potassium channel (hKir2.1) in the paraventricular nucleus of the hypothalamus (PVN) and in the rostral ventrolateral medulla (RVLM) to suppress neuronal excitability, resulted in a long term decrease of blood pressure and sympathetic output in spontaneously hypertensive rats (SHR). Objective: Evaluate gene expression in end-organs of SHR after a chronic overexpression of hKir2.1 channels in either the PVN or RVLM. Methods: mRNA levels of 16 genes known to be involved with blood pressure regulation were evaluated using RT-PCR in tissues from the heart, common carotid artery and kidney of SHR submitted to chronic depression of PVN and RVLM excitability using a lentiviral vector (LVhKir2.1). Results: In SHR hearts in which either the PVN or RVLM were injected with LVhKir2.1, there was a downregulation of angiotensin II receptor 1b (AT1), ATPase, Ca(2+)-transporter, troponin T2 and tropomyosin2 (only in RVLM) relative to the sham group. In the kidney of SHR with LVhKir2.1 injections in PVN and RVLM, angiotensinogen, angiotensin II receptor2 (AT2) and endothelin1 were all upregulated compared to sham. In the carotid artery, endothelin2, endothelin receptor A and B were up-regulated following LVhKir2.1 in to either the PVN or RVLM relative to sham. Conclusion: Chronic overexpression of hKir2.1 channels in PVN and RVLM, promoted a BP decrease with up-regulation of angiotensinogen and AT2 genes expression in the kidney and down-regulation of AT1 in the heart of SHR. Thus, we demonstrate the potential efficacy of central manipulation to protect against end-organ damage in essential hypertension.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (PTDC/SAU-OSM/109081/2008) and Sorin Portugal grants to Isabel Rocha; British Heart Foundation (RG/12/6/29670) and National Institutes of Health (RO1 NS069220). The authors want to acknowledge the technical contributions of Raquel Laires and technical advices of Mafalda Carvalho.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBrain Research 1646 (2016) 109–115pt_PT
dc.identifier.doi10.1016/j.brainres.2016.05.041pt_PT
dc.identifier.issn0006-8993
dc.identifier.urihttp://hdl.handle.net/10451/44104
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/brain-researchpt_PT
dc.subjectmRNApt_PT
dc.subjectHypertensionpt_PT
dc.subjectSympathetic nervous systempt_PT
dc.subjectKidneypt_PT
dc.subjectHeartpt_PT
dc.subjectCommon carotid arterypt_PT
dc.titleReversing gene expression in cardiovascular target organs following chronic depression of the paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in spontaneous hypertensive ratspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/SAU-OSM/109081/2008
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-OSM%2F109081%2F2008/PT
oaire.citation.endPage115pt_PT
oaire.citation.startPage109pt_PT
oaire.citation.titleBrain Researchpt_PT
oaire.citation.volume1646pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameGeraldes
person.familyNameGoncalves Rosa
person.familyNamerocha
person.givenNameVera
person.givenNameNataniel
person.givenNameisabel
person.identifier.ciencia-idD51D-E96C-1633
person.identifier.ciencia-id7313-0C25-7377
person.identifier.orcid0000-0003-1275-3459
person.identifier.orcid0000-0001-5571-8616
person.identifier.orcid0000-0002-7582-0893
person.identifier.ridM-4137-2013
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication33f7ff12-f5ac-408c-954e-773d371a9e12
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