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Impaired renal endothelial nitric oxide synthase and reticulocyte production as modulators of hypertension induced by rHuEPO in the rat

2016-02-25Journal article Restricted access
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dc.contributor.authorRibeiro, Sandra
dc.contributor.authorGarrido, Patrícia
dc.contributor.authorFernandes, João
dc.contributor.authorVala, Helena
dc.contributor.authorRocha-Pereira, Petronila
dc.contributor.authorCosta, Elísio
dc.contributor.authorBelo, Luís
dc.contributor.authorReis, Flávio
dc.contributor.authorSantos-Silva, Alice
dc.date.accessioned2016-04-21T11:17:41Z
dc.date.available2016-04-21T11:17:41Z
dc.date.issued2016-02-25
dc.description.abstractOur aim was to study the effect of a broad range of recombinant human erythropoietin (rHuEPO) doses on hematological and biochemical parameters, blood pressure (BP), renal function and damage in the rat, focusing on endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factors (HIFs). Male Wistar rats were divided in 5 groups receiving different doses of rHuEPO (100, 200, 400 and 600IU/kg body weight (BW)/week) and saline solution (control), during 3weeks. Blood and 24h urine were collected to perform hematological and biochemical analysis. BP was measured by the tail-cuff method. Kidney tissue was collected to mRNA and protein expression assays and to characterize renal lesions. A dose-dependent increase in red blood cells count, hematocrit and hemoglobin levels was found with rHuEPO therapy, in rHuEPO200, rHuEPO400 and rHuEPO600 groups. Increased reticulocyte count was found in rHuEPO400 and rHuEPO600 groups. BP raised in all groups receiving rHuEPO. The rHuEPO200 and rHuEPO600 groups presented increased kidney protein levels of HIF2α, a reduction in kidney protein levels of eNOS, and the highest grade of vascular and tubular renal lesions. Our study showed that rHuEPO-induced hypertension is present before significant hematological changes occur and, therefore, might involve direct (renal) and indirect (hematological) effects, which varies according to the dose used. The presence of renal hypoxia reduces eNOS activity. Excessive erythrocytosis increases blood hyperviscosity, which can be modulated by an increase in reticulocytes. Hypertension leads to early renal damage without alterations in traditional markers of renal function, thus underestimating the serious adverse effects and risks.pt_PT
dc.identifier.citationRibeiro S, Garrido P, Fernandes J, Vala H, Rocha-Pereira P, Costa E, Belo L, Reis F, Santos-Silva (2016). A. Impaired renal endothelial nitric oxide synthase and reticulocyte production as modulators of hypertension induced by rHuEPO in the rat. Life Sciences. 151 (2016) 147–156pt_PT
dc.identifier.doi10.1016/j.lfs.2016.02.088pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.19/3167
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationAgreement PT2020 (UID/MULTI/04378/2013 - POCI/01/0145/FERDER/ 007728, UID/NEU/04539/2013, UID/AGR/04033/2013 - POCI-01-0145- FEDER-006958) and by POPH/FSE (SFRH/BD/61020/2009, SFRH/BD/ 79875/2011 and SFRH/BPD/81968/2011). We would like to thank José Sereno, Filipa Melo and Sara Nunes for all the technical support, and also to CI&DETS and CITABpt_PT
dc.subjectreticulocytespt_PT
dc.subjectrecombinant human erythropoietin therapypt_PT
dc.subjecthypoxiapt_PT
dc.subjectdirect renal vascular effectspt_PT
dc.subjectendothelial nitric oxide synthasept_PT
dc.subjecthypertensionpt_PT
dc.subjectrecombinant human erythropoietin therapypt_PT
dc.titleImpaired renal endothelial nitric oxide synthase and reticulocyte production as modulators of hypertension induced by rHuEPO in the ratpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage156pt_PT
oaire.citation.issue151pt_PT
oaire.citation.startPage147pt_PT
oaire.citation.titleLife Sciencespt_PT
oaire.citation.volume2016pt_PT
person.familyNameVala Correia
person.givenNameHelena Maria
person.identifier.ciencia-id7A1E-E85E-FFA4
person.identifier.orcid0000-0001-6829-4867
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationcdc3d2e2-df06-40ed-8900-1ecbc8a06c8a
relation.isAuthorOfPublication.latestForDiscoverycdc3d2e2-df06-40ed-8900-1ecbc8a06c8a

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