{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:42:36Z","timestamp":1747186956094,"version":"3.40.5"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["LUTS"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Goto\u2010Kakizaki (GK) rats with type 2 diabetes mellitus respond to low temperature (LT) environments with bladder overactivity, including increased voiding frequency and decreased voiding interval and micturition volume. We determined if bladder overactivity could be inhibited by treatment with the combination of a M<jats:sub>3<\/jats:sub>\u2010muscarinic receptor antagonist and a \u03b2<jats:sub>3<\/jats:sub>\u2010adrenergic receptor agonist.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten\u2010week\u2010old female GK rats were fed a high\u2010fat diet for 4\u2009weeks. Cystometric investigations were conducted at room temperature (RT, 27\u2009\u00b1\u20092\u00b0C). The rats were then intraperitoneally administered the vehicle<jats:italic>,<\/jats:italic>the M<jats:sub>3<\/jats:sub>\u2010muscarinic receptor antagonist solifenacin, the \u03b2<jats:sub>3<\/jats:sub>\u2010adrenergic agonist mirabegron, or a combination of solifenacin and mirabegron. Ten minutes after the administrations, the rats were transferred to the LT environment (4\u2009\u00b1\u20092\u00b0C), where the cystometric measurements were continued. The expressions of both M<jats:sub>3<\/jats:sub>\u2010muscarinic and \u03b2<jats:sub>3<\/jats:sub>\u2010adrenergic receptors were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After transfer from RT to LT, both voiding interval and bladder capacity of the vehicle\u2010, solifenacin\u2010, or mirabegron\u2010treated rats were significantly decreased. However, the combination of solifenacin and mirabegron significantly mitigated the bladder overactivity. While both M<jats:sub>3<\/jats:sub>\u2010muscarinic and \u03b2<jats:sub>3<\/jats:sub>\u2010adrenergic receptors were detected, the expression of M<jats:sub>3<\/jats:sub>\u2010muscarinic receptor mRNA was significantly higher than that of \u03b2<jats:sub>3<\/jats:sub>\u2010adrenergic receptor mRNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The cold stress\u2010induced bladder overactivity was not improved by either the M<jats:sub>3<\/jats:sub>\u2010muscarinic receptor antagonist or the \u03b2<jats:sub>3<\/jats:sub>\u2010adrenergic receptor agonist alone. However, the combined treatment mitigated the cold stress responses. Combined therapy with M<jats:sub>3<\/jats:sub>\u2010muscarinic antagonists and \u03b2<jats:sub>3<\/jats:sub>\u2010adrenergic agonists could reduce side effects and improve the quality of life for diabetic patients with bladder overactivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/luts.12472","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T23:03:45Z","timestamp":1671663825000},"page":"68-75","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cold stress\u2010induced bladder overactivity in type 2 diabetic mellitus rats is mitigated by the combination of a<scp>M<sub>3<\/sub><\/scp>\u2010muscarinic antagonist and a \u03b2<sub>3<\/sub>\u2010adrenergic agonist"],"prefix":"10.1111","volume":"15","author":[{"given":"Hiroaki","family":"Hara","sequence":"first","affiliation":[{"name":"Department of Urology Shinshu University School of Medicine Matsumoto 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of Medicine Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruyuki","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Urology Shinshu University School of Medicine Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Ishizuka","sequence":"additional","affiliation":[{"name":"Department of Urology Shinshu University School of Medicine Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2012.02738.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.3760\/cma.j.issn.0366-6999.20132407","article-title":"Diabetic bladder dysfunction","volume":"127","author":"Liu G","year":"2014","journal-title":"Chin Med J 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