RT Journal Article
T1 Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium-dependent vasodilatation of intrarenal arteries
A1 Muñoz Picos, Mercedes
A1 Martínez Sainz, María Del Pilar
A1 López-Oliva Muñoz, María Elvira
A1 Rodríguez Prados, Claudia
A1 César Corbacho, 
A1 Joaquín Carballido, 
A1 García Sacristán, Albino
A1 Hernández Rodríguez, Medardo Vicente
A1 Rivera De Los Arcos, Luis
A1 Javier Saenz-Medina, 
A1 Prieto Ocejo, Dolores
AB The role of NADPH oxidase (Nox)-derived reactive oxygen species in kidney vascular function has extensively been investigated in the harmful context of oxidative stress in diabetes and obesity-associated kidney disease. Since hydrogen peroxide (H2O2) has recently been involved in the non-nitric oxide (NO) non-prostanoid relaxations of intrarenal arteries, the present study was sought to investigate whether NADPH oxidases may be functional sources of vasodilator H2O2 in the kidney and to assess their role in the endothelium-dependent relaxations of human and rat intrarenal arteries. Renal interlobar arteries isolated from the kidney of renal tumor patients who underwent nephrectomy, and from the kidney of Wistar rats, were mounted in microvascular myographs to assess function. Superoxide (O2.-) and H2O2 production was measured by chemiluminescence and Amplex Red fluorescence, and Nox2 and Nox4 enzymes were detected by Western blotting and by double inmunolabeling along with eNOS. Nox2 and Nox4 proteins were expressed in the endothelium of renal arterioles and glomeruli co-localized with eNOS, levels of expression of both enzymes being higher in the cortex than in isolated arteries. Pharmacological inhibition of Nox with apocynin and of CYP 2C epoxygenases with sulfaphenazol, but not of the NO synthase (NOS), reduced renal NADPH-stimulated O2.- and H2O2 production. Under conditions of cyclooxygenase and NOS blockade, acetylcholine induced endothelium-dependent relaxations that were blunted by the non-selective Nox inhibitor apocynin and by the Nox2 or the Nox1/4 inhibitors gp91ds-tat and GKT136901, respectively. Acetylcholine stimulated H2O2 production that was reduced by gp91ds-tat and by GKT136901. These results suggest the specific involvement of Nox4 and Nox2 subunits as physiologically relevant endothelial sources of H2O2 generation that contribute to the endothelium-dependent vasodilatation of renal arteries and therefore have a protective role in kidney vasculature.
PB Elsevier
YR 2018
FD 2018-08-06
LK https://hdl.handle.net/20.500.14352/126129
UL https://hdl.handle.net/20.500.14352/126129
LA eng
NO Muñoz M, Martínez MP, López-Oliva ME, Rodríguez C, Corbacho C, Carballido J, García-Sacristán A, Hernández M, Rivera L, Sáenz-Medina J, Prieto D. Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium-dependent vasodilatation of intrarenal arteries. Redox Biol. 2018 Oct;19:92-104. doi: 10.1016/j.redox.2018.08.004. Epub 2018 Aug 7. PMID: 30125808; PMCID: PMC6105769.
NO Ministerio de Economía y Competitividad (España)
NO Fondo Europeo de Desarrollo Regional (FEDER)
DS Docta Complutense
RD 11 abr 2026