ANG-(3-4) inhibits renal Na+-ATPase in hypertensive rats through a mechanism that involves dissociation of ANG II receptors, heterodimers, and PKA

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dc.contributor.authorDias, Juliana
dc.contributor.authorFerrao, Fernanda M.
dc.contributor.authorAxelband, Flavia
dc.contributor.authorCarmona, Adriana K. [UNIFESP]
dc.contributor.authorLara, Lucienne S.
dc.contributor.authorVieyra, Adalberto
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionNatl Inst Sci & Technol Struct Biol & Bioimaging
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:35:29Z
dc.date.available2016-01-24T14:35:29Z
dc.date.issued2014-04-01
dc.description.abstractThe physiological roles of ANG-(3-4) (Val-Tyr), a potent ANG II-derived peptide, remain largely unknown. the present study 1) investigates whether ANG-(3-4) modulates ouabain-resistant Na+-ATPase resident in proximal tubule cells and 2) verifies whether its possible action on pumping activity, considered the fine tuner of Na+ reabsorption in this nephron segment, depends on blood pressure. ANG-(3-4) inhibited Na+-ATPase activity in membranes of spontaneously hypertensive rats (SHR) at nanomolar concentrations, with no effect in Wistar-Kyoto (WKY) rats or on Na+-K+-ATPase. PD123319 (10(-7) M) and PKA((5-24)) (10(-6) M), an AT(2) receptor (AT(2)R) antagonist and a specific PKA inhibitor, respectively, abrogated this inhibition, indicating that AT(2)R and PKA are central in this pathway. Despite the lack of effect of ANG-(3-4) when assayed alone in WKY rats, the peptide (10(-8) M) completely blocked stimulation of Na+-ATPase induced by 10(-10) M ANG II in normotensive rats through a mechanism that also involves AT(2)R and PKA. Tubular membranes from WKY rats had higher levels of AT(2)R/AT(1)R heterodimers, which remain associated in 10(-10) M ANG II and dissociate to a very low dimerization state upon addition of 10(-8) M ANG-(3-4). This lower level of heterodimers was that found in SHR, and heterodimers did not dissociate when the same concentration of ANG-(3-4) was present. Oral administration of ANG-(3-4) (50 mg/kg body mass) increased urinary Na+ concentration and urinary Na+ excretion with a simultaneous decrease in systolic arterial pressure in SHR, but not in WKY rats. Thus the influence of ANG-(3-4) on Na+ transport and its hypotensive action depend on receptor association and on blood pressure.en
dc.description.affiliationUniv Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, BR-21941902 Rio de Janeiro, Brazil
dc.description.affiliationNatl Inst Sci & Technol Struct Biol & Bioimaging, Rio de Janeiro, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biomed Sci, BR-21941902 Rio de Janeiro, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipBrazilian National Research Council
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipNational Institute of Science and Technology for Structural Biology and Bioimaging, Brazil
dc.description.sponsorshipBrazilian Federal Agency for Support and Evaluation of Graduate Education
dc.description.sponsorshipIDBrazilian National Research Council: 302513/2008-6
dc.description.sponsorshipIDFAPERJ: E-26/102.764/2008
dc.description.sponsorshipIDFAPERJ: E-26/103.050/2012
dc.description.sponsorshipIDFAPESP: 12/50475-2
dc.description.sponsorshipIDNational Institute of Science and Technology for Structural Biology and Bioimaging, Brazil: 573767/2008-4
dc.format.extentF855-F863
dc.identifierhttp://dx.doi.org/10.1152/ajprenal.00488.2013
dc.identifier.citationAmerican Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 306, n. 8, p. F855-F863, 2014.
dc.identifier.doi10.1152/ajprenal.00488.2013
dc.identifier.issn1931-857X
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/37581
dc.identifier.wosWOS:000334610000007
dc.language.isoeng
dc.publisherAmer Physiological Soc
dc.relation.ispartofAmerican Journal of Physiology-renal Physiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectANG-(3-4)en
dc.subjectkidney proximal tubulesen
dc.subjectouabain-resistant Na+-ATPaseen
dc.subjectspontaneously hypertensive ratsen
dc.subjectANG II receptorsen
dc.subjectheterodimerizationen
dc.titleANG-(3-4) inhibits renal Na+-ATPase in hypertensive rats through a mechanism that involves dissociation of ANG II receptors, heterodimers, and PKAen
dc.typeinfo:eu-repo/semantics/article
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