Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium-dependent vasodilatation of intrarenal arteries
| العنوان: | Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium-dependent vasodilatation of intrarenal arteries |
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| المؤلفون: | Dolores Prieto, Joaquín Carballido, César Corbacho, Javier Sáenz-Medina, Albino García-Sacristán, Claudia Rodríguez, Mercedes Muñoz, Medardo Hernández, Luis Rivera, María Elvira López-Oliva, María Pilar Martínez |
| المصدر: | Redox Biology, Vol 19, Iss, Pp 92-104 (2018) Redox Biology |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Clinical Biochemistry, Vasodilation, Kidney, Biochemistry, chemistry.chemical_compound, NOS, nitric oxide synthase, lcsh:QH301-705.5, EDH, endothelium-derived-hyperpolarization, lcsh:R5-920, NADPH oxidase, biology, Chemistry, eNOS, endothelial nitric oxide synthase, NOX4, O2.-, superoxide, Arteries, Middle Aged, medicine.anatomical_structure, NADPH Oxidase 4, H2O2, hydrogen peroxide, PSS, physiological saline solution, NOX1, NADPH Oxidase 2, cardiovascular system, CYP, cytochrome P450, Female, lcsh:Medicine (General), Research Paper, medicine.medical_specialty, ER, endoplasmic reticulum, Nox4, 03 medical and health sciences, ROS, reactive oxygen species, Nox2, SOD, superoxide dismutase, Internal medicine, medicine, Animals, Humans, Rats, Wistar, Aged, NO, nitric oxide, ACh, acetylcholine, EC, endothelial cell, urogenital system, Organic Chemistry, Endothelium-mediated vasodilatation, Hydrogen Peroxide, NADPH, nicotinamide adenine dinucleotide phosphate, medicine.disease, Interlobar arteries, Phe, phenylephrine, COX, cyclooxygenase, 030104 developmental biology, Endocrinology, lcsh:Biology (General), Apocynin, VSM, vascular smooth muscle, biology.protein, Human intrarenal arteries, Endothelium, Vascular, Nox, NADPH oxidase enzymes, Kidney disease |
| الوصف: | 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. Graphical abstract fx1 |
| اللغة: | English |
| تدمد: | 2213-2317 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00f03263c5828e4500117dc7d42f9ceb http://www.sciencedirect.com/science/article/pii/S2213231718306256 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....00f03263c5828e4500117dc7d42f9ceb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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