{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:22:51Z","timestamp":1782512571716,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T00:00:00Z","timestamp":1479686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2017,2]]},"abstract":"\n Objectives<\/jats:title>\n \n To evaluate the expression of the Rho\/Rho\u2010associated protein kinase (\n ROCK<\/jats:styled-content>\n ) pathway in the corpus cavernosum of patients with severe erectile dysfunction (\n ED<\/jats:styled-content>\n ) compared with healthy human corpus cavernosum, and to test the functional effects of two Rho kinase inhibitors (\n RKI<\/jats:styled-content>\n s) on erectile tissue of patients with severe\n ED<\/jats:styled-content>\n , which did not respond to phosphodiesterase type 5 inhibitors (\n PDE<\/jats:styled-content>\n 5Is).\n <\/jats:p>\n <\/jats:sec>\n \n Patients and Methods<\/jats:title>\n \n Human corpus cavernosum samples were obtained after consent from men undergoing penile prosthesis implantation (\n n<\/jats:italic>\n = 7 for organ bath experiments,\n n<\/jats:italic>\n = 17 for quantitative\n PCR<\/jats:styled-content>\n [\n qPCR<\/jats:styled-content>\n ]). Potent control subjects (\n n<\/jats:italic>\n = 5) underwent penile needle biopsy.\n qPCR<\/jats:styled-content>\n was performed for the expression of RhoA and\n ROCK<\/jats:styled-content>\n subtypes 1 and 2. Immunohistochemistry staining against\n ROCK<\/jats:styled-content>\n and \u03b1 smooth muscle actin (\u03b1\n SMA<\/jats:styled-content>\n ) was performed on the corpus cavernosum of patients with\n ED<\/jats:styled-content>\n . Tissue strips were precontracted with phenylephrine and incubated with 1 \u03bc\n m<\/jats:sc>\n of the\n PDE<\/jats:styled-content>\n 5I vardenafil or with\n DMSO<\/jats:styled-content>\n (control). Subsequently, increasing concentrations of the\n RKI<\/jats:styled-content>\n s azaindole or Y\u201027632 were added, and relaxation of tissue was quantified.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The expression of\n ROCK<\/jats:styled-content>\n 1 was unchanged (\n P<\/jats:italic>\n > 0.05), while\n ROCK<\/jats:styled-content>\n 2 (\n P<\/jats:italic>\n < 0.05) was significantly upregulated in patients with\n ED<\/jats:styled-content>\n compared with controls.\n ROCK<\/jats:styled-content>\n 1 and\n ROCK<\/jats:styled-content>\n 2 protein colocalized with \u03b1\n SMA<\/jats:styled-content>\n , confirming the presence of this kinase in cavernous smooth muscle cells and\/or myofibroblasts. After incubation with\n DMSO<\/jats:styled-content>\n , 10 \u03bc\n m<\/jats:sc>\n azaindole and 10 \u03bc\n m<\/jats:sc>\n Y\u201027632 relaxed precontracted tissues with 49.5 \u00b1 7.42% (\n P<\/jats:italic>\n = 0.1470 when compared with vehicle) and 85.9 \u00b1 10.3% (\n P<\/jats:italic>\n = 0.0016 when compared with vehicle), respectively. Additive effects on relaxation of human corpus cavernosum were seen after preincubation with 1 \u03bc\n m<\/jats:sc>\n vardenafil.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The\n RKI<\/jats:styled-content>\n Y\u201027632 causes a significant relaxation of corpus cavernosum in tissue strips of patients with severe\n ED<\/jats:styled-content>\n . The additive effect of vardenafil and Y\u201027632 shows that a combined inhibition of Rho\u2010kinase and phosphodiesterase type 5 could be a promising orally administered treatment for severe\n ED<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bju.13691","type":"journal-article","created":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T10:06:55Z","timestamp":1476958015000},"page":"325-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Additive effects of the Rho kinase inhibitor Y\u201027632 and vardenafil on relaxation of the corpus cavernosum tissue of patients with erectile dysfunction and clinical phosphodiesterase type 5 inhibitor failure"],"prefix":"10.1111","volume":"119","author":[{"given":"Pieter","family":"Uvin","sequence":"first","affiliation":[{"name":"Department of Urology University Hospitals Leuven Leuven Belgium"},{"name":"Department of Urology Jessa Hospital Hasselt University Hasselt Belgium"},{"name":"Department of Development and Regeneration Cluster Organ Systems Faculty of Medicine Group Biomedical Sciences KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Albersen","sequence":"additional","affiliation":[{"name":"Department of Urology University Hospitals Leuven Leuven Belgium"},{"name":"Department of Development and Regeneration Cluster Organ Systems Faculty of Medicine Group Biomedical Sciences KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ine","family":"Bollen","sequence":"additional","affiliation":[{"name":"Physiology Group University of Hasselt Hasselt Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Falter","sequence":"additional","affiliation":[{"name":"Physiology Group University of Hasselt Hasselt Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Weyne","sequence":"additional","affiliation":[{"name":"Department of Urology University Hospitals Leuven Leuven Belgium"},{"name":"Department of Development and Regeneration Cluster Organ Systems Faculty of Medicine Group Biomedical Sciences KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loes","family":"Linsen","sequence":"additional","affiliation":[{"name":"Jessa Hospital University Biobank Limburg Hasselt Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Tinel","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Global Drug Discovery Wuppertal Germany"},{"name":"Institute of Pharmacology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sandner","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Global Drug Discovery Wuppertal Germany"},{"name":"Institute of Pharmacology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinity J.","family":"Bivalacqua","sequence":"additional","affiliation":[{"name":"Department of Urology James Buchanan Brady Urological Institute Johns Hopkins Medical Institutions Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J. 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