RT Journal Article
T1 Activation of the AMP-related kinase (AMPK) induces renal vasodilatation and downregulates Nox-derived reactive oxygen species (ROS) generation
A1 Rodríguez Prados, Claudia
A1 Contreras Jiménez, Cristina
A1 Muñoz Picos, Mercedes
A1 García Sacristán, Albino
A1 Hernández Rodríguez, Medardo Vicente
A1 Rivera De Los Arcos, Luis
A1 Prieto Ocejo, Dolores
A1 Sáenz-Medina, Javier
A1 Corbacho, César
A1 Carballido, Joaquín
A1 López, Miguel
AB AMP-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.
PB Elsevier
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/121932
UL https://hdl.handle.net/20.500.14352/121932
LA eng
NO Rodríguez 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.
NO This 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)
NO Agencia Estatal de Investigación (España)
NO Ministerio de Ciencia e Innovación (España)
NO European Commission
NO Ministerio de Educación, Formación Profesional y Deportes (España)
DS Docta Complutense
RD 20 dic 2025