H2S signaling was 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 was to evaluate the impact of ED on CYS/H2S pathway at functional and molecular level in human penile vascular tissues. NaHS- and CYS-induced responses were evaluated in HCC and HPRA from organ donors without ED (NoED, n = 29) and from ED patients undergoing penile prosthesis insertion (n = 45). cGMP accumulation and cystathionine β-synthase and cystathionine γ-lyase expression were also determined. NaHS-induced relaxations were slightly but significantly impaired in HCC but not in HPRA from ED patients. In contrast, CYS-induced relaxations were markedly impaired in 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 (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 was significantly reduced in HCC from ED patients with respect to NoED. This was confirmed by immunofluorescence in HCC and HPRA sections. 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.
European journal of pharmacology. 2020 Jul 23 [Epub ahead of print]
José M La Fuente, Alejandro Sevilleja-Ortiz, Esther García-Rojo, Mariam El Assar, Argentina Fernández, Augusto J Pepe-Cardoso, Juan I Martínez-Salamanca, Javier Romero-Otero, Leocadio Rodríguez-Mañas, Javier Angulo
Serviço de Urologia, Hospital Santo Antonio, Porto, Portugal., Servicio de Histología-Investigación, Hospital Universitario Ramón y Cajal - IRYCIS, Madrid, Spain., Servicio de Urología, Hospital Universitario Doce de Octubre, Madrid, Spain., FIBio Hospital Universitario de Getafe, Getafe, Spain., Serviço de Urologia, Hospital Fernando da Fonseca, Amadora-Sintra, Portugal., Servicio de Urología, Hospital Universitario Puerta de Hierro, Majadahonda, Spain., Servicio de Geriatría, Hospital Universitario de Getafe, Getafe, Spain., Servicio de Histología-Investigación, Hospital Universitario Ramón y Cajal - IRYCIS, Madrid, Spain. Electronic address: .