2026-06-29T02:38:56Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1259562025-11-13T01:11:27Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Gomez del Val, Alfonso author Sánchez, Ana author Freire-Agulleiro, Óscar author Martínez, María Pilar author Olmos, Lucia author Sanez Medina, Javier author Comerma-Steffensen, Simon Gabriel author Simonsen, Ulf author Rivera, Luis author López, Miguel author Muñoz Picos, Mercedes author Contreras Jiménez, Cristina author Prieto Ocejo, Dolores author 2025 Objective Erectile dysfunction (ED) is considered an early manifestation of cardiovascular disease (CVD), endothelial dysfunction being the link between CVD and vasculogenic ED. Mitochondrial reactive oxygen species (mtROS) have been involved in the vascular complications of metabolic disorders. The aim of this study was to assess the impact of obesity on endothelial function, redox metabolism and mitochondrial bioenergetics of penile erectile tissue. Methods Wistar rats were fed a high-fat diet (HFD) or standard diet (STD), and penile vascular function was assessed in microvascular myographs. mtROS levels were measured by mitoSOX (O2.-) and Amplex Red (H2O2) fluorimetry, and the effect of the mitochondrial antioxidant mitoTempo on endothelium-dependent relaxations was tested. Mitochondrial respiration of intact microarteries was assessed with an Agilent Seahorse XF Pro analyzer, and the expression of mitochondria redox regulators was analysed by Western blot. Results Endothelium-dependent relaxations to acetylcholine (ACh) and to the mitoKATP channel activator BMS191095 were reduced in penile arteries from HFD. mtROS levels were significantly increased and associated with upregulation of the endothelial NADPH oxidase 4 (Nox4) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in HFD erectile tissue. MitoTempo inhibited endothelial relaxations in control and HFD penile arteries. The bioenergetic profile was significantly reduced in HFD penile arteries compared to STD rats. Conclusions Mitochondrial dysfunction with impaired bioenergetics and reduced mitoKATP channel-mediated relaxation underlie endothelial and vascular dysfunction of erectile tissue in obesity, despite a compensatory mechanism that enhances Nox4-derived endothelial vasodilator mtROS. Therapeutic strategies aimed to stabilize mitochondria could restore redox balance and improve mitochondrial bioenergetics thus preventing oxidative stress and vascular dysfunction underlying metabolic disease associated ED. Gómez Del Val A, Sánchez A, Freire-Agulleiro Ó, et al. Penile endothelial dysfunction, impaired redox metabolism and blunted mitochondrial bioenergetics in diet-induced obesity: Compensatory role of H2O2. Free Radical Biology and Medicine 2025;230:222–33. https://doi.org/10.1016/j.freeradbiomed.2025.02.004 0891-5849 10.1016/j.freeradbiomed.2025.02.004 https://hdl.handle.net/20.500.14352/125956 https://doi.org/10.1016/j.freeradbiomed.2025.02.004 https://www.sciencedirect.com/science/article/pii/S0891584925000796?via%3Dihub Penile endothelial dysfunction, impaired redox metabolism and blunted mitochondrial bioenergetics in diet-induced obesity: Compensatory role of H2O2