MP45-05 ACTIVATION OF NRF2 IMPROVES ENDOTHELIAL FUNCTION IN CORPUS CAVERNOSUM FROM AGED RATS AND IN CORPUS CAVERNOSUM AND PENILE ARTERIES FROM ED PATIENTS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology I1 Apr 2017MP45-05 ACTIVATION OF NRF2 IMPROVES ENDOTHELIAL FUNCTION IN CORPUS CAVERNOSUM FROM AGED RATS AND IN CORPUS CAVERNOSUM AND PENILE ARTERIES FROM ED PATIENTS Juan Ignacio Martínez-Salamanca, Mariam El Assar, Argentina Fernández, Alberto Sánchez-Ferrer, Agustín Fraile, Leocadio Rodríguez-Mañas, Joaquín Carballido, and Javier Angulo Juan Ignacio Martínez-SalamancaJuan Ignacio Martínez-Salamanca More articles by this author , Mariam El AssarMariam El Assar More articles by this author , Argentina FernándezArgentina Fernández More articles by this author , Alberto Sánchez-FerrerAlberto Sánchez-Ferrer More articles by this author , Agustín FraileAgustín Fraile More articles by this author , Leocadio Rodríguez-MañasLeocadio Rodríguez-Mañas More articles by this author , Joaquín CarballidoJoaquín Carballido More articles by this author , and Javier AnguloJavier Angulo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1423AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adequate antioxidant response is essential for tissue homeostasis and function. However, systems responsible for antioxidant response are down-regulated in some pathological situations and aging. This is the case for Nrf2 that orchestrates cellular response to oxidative stress. The aim was to evaluate pharmacological activation of Nrf2 on the impairment of endothelial relaxation and reactive oxygen species-induced responses in corpus cavernosum (CC) from aged rats and in CC and penile arteries from patients with erectile dysfunction (ED). METHODS Endothelium-dependent relaxations to carbachol and responses to H2O2 were evaluated in CC from 3-months (young) and 20-months (aged) old rats in the absence or the presence of the Nrf2-activators, sulforaphane (10 microM) and oltipraz (30 microM). Upregulation of Nrf2 was assessed by ELISA. The effects of these Nrf2-activators were also evaluated on endothelial relaxation and H2O2-induced responses in human corpus cavernosum (HCC) and penile resistance arteries (HPRA) obtained from patients undergoing penile prosthesis implantation. RESULTS Aged rats CC displayed ED and impaired endothelium-dependent and H2O2-induced relaxation. Ex vivo exposure to either sulforaphane or oltipraz improved endothelial and H2O2-induced relaxation of CC from aged rats. HCC and HPRA were obtained from 19 patients (age: 60.7+/-2.0 years, hypertension: 8, dyslipidemia: 7, diabetes: 6, CVD: 4, obesity: 2). Treatment with sulforaphane improved endothelium-dependent (pD2 for acetylcholine: 5.18+/-0.28 vs 6.34+/-0.37∗) as well as neurogenic relaxation (Emax: 45.7+/-6.4% vs 60.9+/-3.0%∗) in HCC. Sulforaphane also improved endothelial (pD2 for acetylcholine: 5.82+/-0.38 vs 7.21+/-0.32∗) and H2O2-induced vasodilation in HPRA (pD2 for H2O2: 4.13+/-0.13 vs 5.07+/-0.17∗). Positive effects of Nrf2-activation were confirmed by the improvement of endothelial vasodilation driven by oltipraz in HPRA. CONCLUSIONS Pharmacological activation of Nrf2 improves cavernosal function in aged animals with ED. These effects were confirmed in human tissue, including penile arteries, from patients with ED, suggesting that Nrf2 activation could be a reasonable target for the management of ED. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e613 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Juan Ignacio Martínez-Salamanca More articles by this author Mariam El Assar More articles by this author Argentina Fernández More articles by this author Alberto Sánchez-Ferrer More articles by this author Agustín Fraile More articles by this author Leocadio Rodríguez-Mañas More articles by this author Joaquín Carballido More articles by this author Javier Angulo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...