RT Journal Article
T1 Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress
A1 Saenz-Medina, Javier
A1 Muñoz Picos, Mercedes
A1 Rodríguez Prados, Claudia
A1 Contreras Jiménez, Cristina
A1 Sánchez Pina, Ana Alejandra
A1 Coronado, María José
A1 Ramil, Elvira
A1 Santos, Martin
A1 Carballido, Joaquín
A1 Prieto, Dolores
AB Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The aim of the present study was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis. Experimental approach: Endothelial dysfunction was assessed in preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and mRNA and protein expression by RT-PCR and immunofluorescence, respectively. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR. Results: Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses and normalized NADPH oxidase-dependent higher superoxide values of renal cortex from the hyperoxaluric group. Conclusions: The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.
PB MDPI
SN 2073-4409
YR 2022
FD 2022-07-27
LK https://hdl.handle.net/20.500.14352/124983
UL https://hdl.handle.net/20.500.14352/124983
LA eng
NO Saenz-Medina, J.; Muñoz, M.; Rodriguez, C.; Contreras, C.; Sánchez, A.; Coronado, M.J.; Ramil, E.; Santos, M.; Carballido, J.; Prieto, D. Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress. Cells 2022, 11, 2306. https://doi.org/10.3390/cells11152306
NO Submission received: 18 June 2022 / Revised: 15 July 2022 / Accepted: 24 July 2022 / Published: 27 July 2022.This research was funded by by a 2017 AEU research grant from the Spanish Urological Association and PID2019-105689RB. Ministerio de Ciencia e Innovación (Spain) co-funded by the FEDER program of the EU.
NO Asociación Española de Urología
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 18 dic 2025