MP84-09 DEFECTIVE L-CYSTEINE/HYDROGEN SULFIDE PATHWAY IN HUMAN CORPUS CAVERNOSUM AND PENILE ARTERIES FROM MEN WITH ERECTILE DYSFUNCTION

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP84)1 Apr 2020MP84-09 DEFECTIVE L-CYSTEINE/HYDROGEN SULFIDE PATHWAY IN HUMAN CORPUS CAVERNOSUM AND PENILE ARTERIES FROM MEN WITH ERECTILE DYSFUNCTION Alejandro Sevilleja-Ortiz, José M. La Fuente, Juan Ignacio Martínez-Salamanca*, Esaú Fernández-Pascual, Joaquín Carballido, and Javier Angulo Alejandro Sevilleja-OrtizAlejandro Sevilleja-Ortiz More articles by this author , José M. La FuenteJosé M. La Fuente More articles by this author , Juan Ignacio Martínez-Salamanca*Juan Ignacio Martínez-Salamanca* More articles by this author , Esaú Fernández-PascualEsaú Fernández-Pascual 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/10.1097/JU.0000000000000976.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hydrogen sulfide (H2S) signaling has been proposed to participate in erectile physiology. L-cysteine (CYS)/H2S pathway stimulation causes cGMP-dependent relaxation of human corpus cavernosum (HCC) and penile arteries (HPRA). The aim of this work was to evaluate the impact of erectile dysfunction (ED) on CYS/H2S pathway at functional and molecular level in human penile vascular tissues. METHODS: NaHS- and CYS-induced responses were evaluated in HCC and HPRA from organ donors without notice of ED (NoED, n=29) and from ED patients undergoing penile prosthesis insertion (n=45). cGMP accumulation and cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) expressions were also determined in these tissues. RESULTS: NaHS-induced relaxations were slightly but significantly impaired in HCC (pEC50 4.58±0.09 vs. 4.19±0.07, p<0.01) but not in HPRA (pEC50 4.16±0.10 vs. 4.00±0.07) from ED patients. In contrast, CYS-induced relaxations were markedly impaired in both HCC (Emax 67.6±4.9% vs 46.2±4.6%, p<0.01) and HPRA (Emax 80.8±4.0% vs 48.1±8.6%, p<0.05) from men with ED. Impairment of CYS-induced responses was observed even after separating diabetic ED patients. In HPRA from ED patients, CYS- but not NaHS-induced vasodilation was significantly associated to endothelial function measured as vasodilatory capacity of acetylcholine (ACh) in these preparations (pEC25 CYS vs. Emax ACh: r2=0.481, p<0.01). Impairment of CYS-induced relaxations was related to significant reduction in CYS-induced accumulation of cGMP in cavernosal tissue. Furthermore, the expression of H2S synthesizing enzymes CBS and CSE, as determined by Western blot, was significantly reduced in HCC from ED patients with respect to NoED tissues. This diminished expression of CBS and CSE was clearly manifested in immunofluorescence assays in HCC and HPRA sections. CONCLUSIONS: ED involves impairment of CYS/H2S pathway in penile vascular tissues associated with decreased expression of H2S generating enzymes, CBS and CSE. These evidences support a therapeutic potential for modulation of CYS/H2S signaling in the management of ED. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1268-e1268 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alejandro Sevilleja-Ortiz More articles by this author José M. La Fuente More articles by this author Juan Ignacio Martínez-Salamanca* More articles by this author Esaú Fernández-Pascual More articles by this author Joaquín Carballido More articles by this author Javier Angulo More articles by this author Expand All Advertisement PDF downloadLoading ...