{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:33:37Z","timestamp":1783046017502,"version":"3.54.6"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Economy and Competitiveness","award":["PI15\/01160"],"award-info":[{"award-number":["PI15\/01160"]}]},{"name":"the Ministry of Economy and Competitiveness","award":["PI23\/00877"],"award-info":[{"award-number":["PI23\/00877"]}]},{"name":"the Ministry of Economy and Competitiveness","award":["CIBERFES CB16\/10\/00464"],"award-info":[{"award-number":["CIBERFES CB16\/10\/00464"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Canonical transient receptor potential (TRPC) channels contribute to calcium homeostasis, which is involved in penile vascular contractility and erectile dysfunction (ED) pathophysiology. We evaluated the impact of TRPC5 inhibition on endothelial function in penile vascular tissue from aging rats and ED patients and its effect on the relaxant efficacy of PDE5 inhibitors. TRPC inhibitor-induced endothelial and neurogenic relaxations were evaluated in corpus cavernosum (RCC) from a rat model of aging-related ED and in human penile resistance arteries (HPRAs) and corpus cavernosum (HCC) from ED patients and organ donors (NoED). The TRPC5 inhibitor, AC1903, was more effective than TRPC3 and TRPC4 inhibitors in relaxing aged RCC and HCC and HPRA from ED patients. In addition to enhancing endothelial and neurogenic relaxations in RCC from aged animals, AC1903 improved endothelium-dependent relaxation in both HCC and HPRA from ED patients but not in tissues from NoED. Cavernosal expression of TRPC5 was not different between ED and NoED subjects. AC1903 potentiated relaxations to the PDE5 inhibitor, tadalafil, in HCC\/HPRA from ED patients. TRPC5 inhibition improved penile vascular function in aged rats and patients with ED. TRPC5 inhibition could be a potential therapeutic target for ED, particularly when combined with PDE5 inhibitors to enhance treatment outcomes.<\/jats:p>","DOI":"10.3390\/ijms26041431","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T04:44:03Z","timestamp":1739162643000},"page":"1431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting TRPC-5 Channel Inhibition to Improve Penile Vascular Function in Erectile Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"given":"Mariam","family":"El Assar","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital de Getafe, 28905 Getafe, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n IdiPaz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Garc\u00eda-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Urology, Hospital Universitario 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"La Fuente","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Urologia, Centro Hospitalar e Universit\u00e1rio de Santo Ant\u00f3nio (CHUdSA), 4099-001 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3809-2097","authenticated-orcid":false,"given":"Manuel","family":"Alonso-Isa","sequence":"additional","affiliation":[{"name":"Department of Urology, Hospital Universitario 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2318-9064","authenticated-orcid":false,"given":"Juan I.","family":"Mart\u00ednez-Salamanca","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argentina","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda\u2014IRYCIS\/UFV, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-3724","authenticated-orcid":false,"given":"Patricia","family":"Sosa","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital de Getafe, 28905 Getafe, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n IdiPaz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Romero-Otero","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitario HM Sanchinarro, HM Hospitales, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-1333","authenticated-orcid":false,"given":"Leocadio","family":"Rodr\u00edguez-Ma\u00f1as","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n IdiPaz, 28046 Madrid, Spain"},{"name":"Servicio de Geriatr\u00eda, Hospital Universitario de Getafe, 28905 Getafe, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-9465","authenticated-orcid":false,"given":"Javier","family":"Angulo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda\u2014IRYCIS\/UFV, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5534\/wjmh.2016.34.2.89","article-title":"Modifying Risk Factors in the Management of Erectile Dysfunction: A Review","volume":"34","author":"DeLay","year":"2016","journal-title":"World J. 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