{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:12:43Z","timestamp":1772856763498,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007113","name":"Sexual Medicine Society of North America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007113","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2016,9]]},"abstract":"\n Objective<\/jats:title>\n \n To examine the effects of mirabegron, a selective \u03b2\n 3<\/jats:sub>\n \u2010adrenoceptor agonist that has recently been approved for the treatment of overactive bladder (\n OAB<\/jats:styled-content>\n ), on erectile function. Stimulation of \u03b2\n 3<\/jats:sub>\n \u2010adrenoceptors localised in cavernosal smooth muscle cells may play a physiological role in mediating penile erection, and offer a beneficial pharmacological action for patients who have\n OAB<\/jats:styled-content>\n and erectile dysfunction (\n ED<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n Corpus cavernosal (\n CC<\/jats:styled-content>\n ) specimens were obtained from patients with\n ED<\/jats:styled-content>\n and Peyronie's disease undergoing penile prosthesis implantation. Erectile responses were also evaluated\n in vivo<\/jats:italic>\n after intracavernosal injection (\n ICI<\/jats:styled-content>\n ) of mirabegron in anaesthetised rats. Mirabegron\u2010elicited relaxation responses (10\n \u20138<\/jats:sup>\n \u201310\n \u20133<\/jats:sup>\n m<\/jats:sc>\n ) on phenylephrine\u2010induced contraction were seen in human\n CC<\/jats:styled-content>\n (\n HCC<\/jats:styled-content>\n ) and rat\n CC<\/jats:styled-content>\n strips in isolated organ\u2010bath studies. The effects of inhibitors, namely L\u2010\n NAME<\/jats:styled-content>\n [\n \n N\n G<\/jats:sup>\n <\/jats:styled-content>\n \u2010nitro\u2010L\u2010arginine methyl ester, a competitive inhibitor of nitric oxide synthase (\n NOS<\/jats:styled-content>\n ), 100 \u03bc\n m<\/jats:sc>\n ],\n ODQ<\/jats:styled-content>\n [1H\u2010(1,2,4) oxadiazolo(4,3\u2010\u03b1) quinoxalin\u20101\u2010one, a soluble guanylyl cyclase (\n sGC<\/jats:styled-content>\n ) inhibitor, 30\u03bc\n m<\/jats:sc>\n ], methylene blue (a NOS and\n sGC<\/jats:styled-content>\n inhibitor, 20\u03bc\n m<\/jats:sc>\n ),\n SR<\/jats:styled-content>\n 59230A (\u03b2\n 3<\/jats:sub>\n \u2010adrenoceptor blocker, 1 \u03bc\n m<\/jats:sc>\n ), and fasudil [Rho\u2010associated protein kinase (\n ROCK<\/jats:styled-content>\n ) inhibitor, 0.1 \u03bc\n m<\/jats:sc>\n ], on mirabegron\u2010induced relaxation responses were evaluated. Responses to mirabegron were compared with responses to isoprenaline and nebivolol. Immunohistochemistry was used to localise \u03b2\n 3<\/jats:sub>\n \u2010adrenoceptors and\n ROCK<\/jats:styled-content>\n in\n CC<\/jats:styled-content>\n smooth muscle cells.\n In vivo<\/jats:italic>\n rat data were expressed as intracavernosal pressure (\n ICP<\/jats:styled-content>\n )\/mean arterial pressure, and total ICP.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Mirabegron resulted in a relaxation of phenylephrine\u2010evoked\n CC<\/jats:styled-content>\n contractions in a concentration\u2010dependent manner and\n SR<\/jats:styled-content>\n 59230A antagonised the mirabegron\u2010induced relaxations in\n HCC<\/jats:styled-content>\n and rat\n CC<\/jats:styled-content>\n . Other inhibitors, L\u2010\n NAME<\/jats:styled-content>\n ,\n ODQ<\/jats:styled-content>\n , and methylene blue, did not affect the mirabegron\u2010induced relaxation responses. Mirabegron relaxation responses at concentrations (0.1\u201310 \u03bc\n m<\/jats:sc>\n ) were enhanced by fasudil (\n ROCK<\/jats:styled-content>\n inhibitor) in rat but not in\n HCC<\/jats:styled-content>\n strips.\n KC<\/jats:styled-content>\n l\u2010induced contractions in\n HCC<\/jats:styled-content>\n and rat\n CC<\/jats:styled-content>\n were partially inhibited by mirabegron.\n In vivo,<\/jats:italic>\n ICI<\/jats:styled-content>\n of mirabegron (doses of 0.1\u20131 mg\/kg) had a minor effect on\n ICP<\/jats:styled-content>\n when compared with vehicle administration. Immunohistochemistry data showed \u03b2\n 3<\/jats:sub>\n \u2010adrenoceptors localised in the smooth muscle cells of the\n HCC<\/jats:styled-content>\n and rat\n CC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Mirabegron markedly relaxed isolated\n CC<\/jats:styled-content>\n strips by activating \u03b2\n 3<\/jats:sub>\n \u2010adrenoceptors independently of the\n NO<\/jats:styled-content>\n \u2010\n cGMP<\/jats:styled-content>\n pathway. There is also evidence of the existence of a close functional link between \u03b2\n 3<\/jats:sub>\n \u2010adrenoceptors and the RhoA\/\n ROCK<\/jats:styled-content>\n pathway. These results may support further clinical studies using combinations of mirabegron with\n ROCK<\/jats:styled-content>\n and phosphodiesterase type 5 inhibitors (\n PDE<\/jats:styled-content>\n 5i) for the treatment of\n ED<\/jats:styled-content>\n , especially in patients who do not respond to\n PDE<\/jats:styled-content>\n 5i therapy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bju.13515","type":"journal-article","created":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T17:29:12Z","timestamp":1461950952000},"page":"464-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Mirabegron causes relaxation of human and rat corpus cavernosum: could it be a potential therapy for erectile dysfunction?"],"prefix":"10.1111","volume":"118","author":[{"given":"Serap","family":"Gur","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmacy Ankara University Ankara Turkey"},{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"Peak","sequence":"additional","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faysal A.","family":"Yafi","sequence":"additional","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip J.","family":"Kadowitz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh C.","family":"Sikka","sequence":"additional","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA 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