Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure

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dc.citation.volume7
dc.contributor.authorArruda-Junior, Daniel F.
dc.contributor.authorMartins, Flavia L.
dc.contributor.authorDariolli, Rafael
dc.contributor.authorJensen, Leonardo
dc.contributor.authorAntonio, Ednei L. [UNIFESP]
dc.contributor.authordos Santos, Leonardo
dc.contributor.authorTucci, Paulo J. F. [UNIFESP]
dc.contributor.authorGirardi, Adriana C. C.
dc.coverageLausanne
dc.date.accessioned2020-08-14T13:44:13Z
dc.date.available2020-08-14T13:44:13Z
dc.date.issued2016
dc.description.abstractCirculating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 +/- 5 vs. 45 +/- 3%, p < 0.05), and the isovolumic relaxation time decreased (33 +/- 2 vs. 27 +/- 1 msen
dc.description.abstractp < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow. GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with upregulation of the apical proximal tubule endocytic receptor megalin and of the podocyte main slit diaphragm proteins nephrin and podocin. Collectively, these findings demonstrate that DPPIV inhibition exerts renoprotective effects and ameliorates cardiorenal function in rats with established HF. Long-term studies with DPPIV inhibitors are needed to ascertain whether these effects ultimately translate into improved clinical outcomes.en
dc.description.affiliationUniv Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Med, Div Cardiol, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Espirito Santo, Dept Physiol Sci, Vitoria, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Med, Div Cardiol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipIDFAPESP: 2013/10619-8
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fphys.2016.00293
dc.identifier.citationFrontiers In Physiology. Lausanne, v. 7, p. -, 2016.
dc.identifier.doi10.3389/fphys.2016.00293
dc.identifier.fileWOS000379416500001.pdf
dc.identifier.issn1664-042X
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57545
dc.identifier.wosWOS:000379416500001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Physiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectvildagliptinen
dc.subjectcardiorenal dysfunctionen
dc.subjectfluid retentionen
dc.subjectglucagon-like peptide-1en
dc.subjectproteinuriaen
dc.subjectmegalinen
dc.titleDipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failureen
dc.typeinfo:eu-repo/semantics/article
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