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Activation of the AMP-related kinase (AMPK) induces renal vasodilatation and downregulates Nox-derived reactive oxygen species (ROS) generation

dc.contributor.authorRodríguez Prados, Claudia
dc.contributor.authorContreras Jiménez, Cristina
dc.contributor.authorMuñoz Picos, Mercedes
dc.contributor.authorGarcía Sacristán, Albino
dc.contributor.authorHernández Rodríguez, Medardo Vicente
dc.contributor.authorRivera De Los Arcos, Luis
dc.contributor.authorPrieto Ocejo, Dolores
dc.contributor.authorSáenz-Medina, Javier
dc.contributor.authorCorbacho, César
dc.contributor.authorCarballido, Joaquín
dc.contributor.authorLópez, Miguel
dc.date.accessioned2025-06-27T10:00:10Z
dc.date.available2025-06-27T10:00:10Z
dc.date.issued2020
dc.descriptionThis work was supported by Ministerio de Ciencia e Innovacion (Spain) co-funded by the FEDER Program of EU (grants nº SAF2016-77526-R and RTI2018-101840-B-I00). Claudia Rodríguez was supported by grant FPU16/04582 from MECD (Spain)
dc.description.abstractAMP-activated protein kinase (AMPK) is a cellular energy sensor activated during energy stress to stimulate ATP production pathways and restore homeostasis. AMPK is widely expressed in the kidney and involved in mitochondrial protection and biogenesis upon acute renal ischemia, AMPK activity being blunted in metabolic disease-associated kidney disease. Since little is known about AMPK in the regulation of renal blood flow, the present study aimed to assess the role of AMPK in renal vascular function. Functional responses to the selective AMPK activator A769662 were assessed in intrarenal small arteries isolated from the kidney of renal tumour patients and Wistar rats and mounted in microvascular myographs to perform simultaneous measurements of intracellular calcium [Ca] and tension. Superoxide (O) and hydrogen peroxide (HO) production were measured by chemiluminescence and fluorescence and protein expression by Western blot. Activation of AMPK with A769662 increased AMPK phosphorylation at Thr-172 and induced potent relaxations compared to AICAR in isolated human and rat intrarenal arteries, through both endothelium-dependent mechanisms involving nitric oxide (NO) and intermediate-conductance calcium-activated potassium (IK) channels, as well as activation of ATP-sensitive (K) channels and sarcoplasmic reticulum Ca-ATP (SERCA) in vascular smooth muscle (VSM). Furthermore, AMPK activator reduced NADPH oxidase 4 (Nox4) and Nox2-derived reactive oxygen species (ROS) production. These results demonstrate that A769662 has potent vasodilator and antioxidant effects in intrarenal arteries. The benefits of AMPK activation in rat kidney are reproduced in human arteries and therefore vascular AMPK activation might be a therapeutic target in the treatment of metabolic disease-associated kidney injury.
dc.description.departmentDepto. de Fisiología
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipAgencia Estatal de Investigación (España)
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipMinisterio de Educación, Formación Profesional y Deportes (España)
dc.description.statuspub
dc.identifier.citationRodríguez C, Contreras C, Sáenz-Medina J, Muñoz M, Corbacho C, Carballido J, et al. Activation of the AMP-related kinase (AMPK) induces renal vasodilatation and downregulates Nox-derived reactive oxygen species (ROS) generation. Redox Biology 2020;34:101575. https://doi.org/10.1016/j.redox.2020.101575.
dc.identifier.doi10.1016/j.redox.2020.101575
dc.identifier.officialurlhttps://doi.org/10.1016/j.redox.2020.101575
dc.identifier.pmid32470915
dc.identifier.urihttps://hdl.handle.net/20.500.14352/121932
dc.journal.titleRedox Biology
dc.language.isoeng
dc.publisherElsevier
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-101840-B-I00/ES/AMPKALPHA HIPOTALAMICA Y BALANCE ENERGETICO/
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-77526-R
dc.relation.projectIDinfo:eu-repo/grantAgreement/MECD//FPU16%2F04582/ES/FPU16%2F04582/
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu612
dc.subject.cdu616.61
dc.subject.keywordAMPK activators
dc.subject.keywordIK(Ca) channels
dc.subject.keywordK(ATP) channels
dc.subject.keywordReactive oxygen species
dc.subject.keywordRenal arteries
dc.subject.keywordSERCA
dc.subject.ucmCiencias Biomédicas
dc.subject.ucmFisiología
dc.subject.ucmNefrología y urología
dc.subject.unesco2411 Fisiología Humana
dc.subject.unesco3205.06 Nefrología
dc.titleActivation of the AMP-related kinase (AMPK) induces renal vasodilatation and downregulates Nox-derived reactive oxygen species (ROS) generation
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number34
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscoveryd9701394-5dd8-487b-885e-c860c306f959

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