2026-06-27T22:46:00Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/47102024-07-30T15:21:56Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Muñoz Picos, Mercedes author López-Oliva Muñoz, María Elvira author Pinilla Pérez, Estéfano author Rodríguez Prados, Claudia author Martínez Saiz, María Pilar author Contreras Jiménez, Cristina author Gómez, Alfonso author Benedito Castellote, Sara author Sáenz Medina, Javier author Rivera De Los Arcos, Luis author Prieto Ocejo, Dolores 2023-06-16T14:19:53Z 2023-06-16T14:19:53Z 2021-11-22 0006-2952 10.1016/j.bcp.2021.114850 https://hdl.handle.net/20.500.14352/4710 https://doi.org/10.1016/j.bcp.2021.114850 Arachidonic acid (AA)-derived cytochrome P450 (CYP) derivatives, epoxyeicosatrienoic acids (EETs) and 20-hidroxyeicosatetranoic acid (20-HETE), play a key role in kidney tubular and vascular functions and blood pressure. Altered metabolism of CYP epoxygenases and CYP hydroxylases has differentially been involved in the pathogenesis of metabolic disease-associated vascular complications, although the mechanisms responsible for the vascular injury are unclear. The present study aimed to assess whether obesity-induced changes in CYP enzymes may contribute to oxidative stress and endothelial dysfunction in kidney preglomerular arteries. Endothelial function and reactive oxygen species (ROS) production were assessed in interlobar arteries of obese Zucker rats (OZR) and their lean counterparts lean Zucker rats (LZR) and the effects of CYP2C and CYP4A inhibitors sulfaphenazole and HET0016, respectively, were examined on the endothelium-dependent relaxations and O2 − and H2O2 levels of preglomerular arteries. Non-nitric oxide (NO) non-prostanoid endothelium-derived hyperpolarization (EDH)-type responses were preserved but resistant to the CYP epoxygenase blocker sulfaphenazole in OZR in contrast to those in LZR. Sulfaphenazole did not further inhibit reduced arterial H2O2 levels, and CYP2C11/CYP2C23 enzymes were downregulated in intrarenal arteries from OZR. Renal EDH-mediated relaxations were preserved in obese rats by the enhanced activity and expression of endothelial calcium-activated potassium channels (KCa). CYP4A blockade restored impaired NO-mediated dilatation and inhibited augmented O2 − production in kidney arteries from OZR. The current data demonstrate that both decreased endothelial CYP2C11/ CYP2C23-derived vasodilator H2O2 and augmented CYP4A-derived 20-HETE contribute to endothelial dysfunction and vascular oxidative stress in obesity. CYP4A inhibitors ameliorate arterial oxidative stress and restore endothelial function which suggests its therapeutic potential for the vascular complications of obesity-associated kidney injury. eng Atribución-NoComercial-SinDerivadas 3.0 España Differential contribution of renal cytochrome P450 enzymes to kidney endothelial dysfunction and vascular oxidative stress in obesity journal article URL https://docta.ucm.es/bitstreams/0bdc654e-2343-457c-a6fd-874484e4a575/download File MD5 3acd212531a9091ab8544e864137c97b 7493522 application/pdf 1-s2.0-S0006295221004664-main.pdf URL https://docta.ucm.es/bitstreams/3549e4e9-b0bf-484b-83f5-4b510685b301/download File MD5 f7414e0728179c0edbd6249deb6b744b 75850 text/plain 1-s2.0-S0006295221004664-main.pdf.txt