{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T04:36:26Z","timestamp":1754109386591,"version":"3.37.3"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["FAPESP 2018\/09765\u20103","FAPESP 2017\/15175\u20101"],"award-info":[{"award-number":["FAPESP 2018\/09765\u20103","FAPESP 2017\/15175\u20101"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the functional and molecular alterations of contractile and relaxant machinery in the bladder and urethra that lead to the underactive bladder (UAB) in old female mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female young (3\u2010months) and old (18\u2010months) C57BL\/6 mice were used. Urodynamic was assessed in awake and anaesthetized mice. Electrical\u2010field stimulation (EFS) and concentration\u2010response curves to contractile and relaxing agents in isolated bladders and urethras were performed. Messenger RNA (mRNA) expressions of muscarinic, adrenergic, and transient receptor potential vanilloid\u20104 (TRPV4), and of the enzymes tyrosine hydroxylase and neuronal nitric oxide synthase (nNOS) were determined. Bladder cyclic adenosine monophosphate (cAMP) levels were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cystometry in old mice showed incapacity to produce bladder emptying. On filter paper, old mice showed reduced urinary spots. Compared to the young group, bladder contractions induced by EFS and carbachol were lower in old mice. The \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor agonist mirabegron promoted higher bladder relaxation and elevation of cAMP levels in old mice. In old mice urethras, the \u03b1<jats:sub>1a<\/jats:sub>\u2010adrenoceptor agonist phenylephrine produced higher contractions, but no differences were found for the NO donor sodium nitroprusside\u2010induced relaxations. In old mice, increased mRNA expressions of \u03b2<jats:sub>3<\/jats:sub>\u2010 and \u03b1<jats:sub>1a<\/jats:sub>\u2010adrenoceptors in bladder and urethra were found, respectively, whereas the muscarinic M<jats:sub>2<\/jats:sub> and M<jats:sub>3<\/jats:sub> receptors and \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptors did not change between groups. Reduced mRNA expressions of tyrosine hydroxylase and nNOS were found in old mouse urethras. Additionally, TRPV4 expression was reduced in bladder urothelium from old mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Age\u2010associated mouse UAB is the result of autonomic dysfunction at multiple levels leading to the less sensitive and overrelaxed bladder, along with urethral hypercontractility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.23990","type":"journal-article","created":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T09:22:07Z","timestamp":1554110527000},"page":"1212-1221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Autonomic dysregulation at multiple sites is implicated in age\u2010associated underactive bladder in female mice"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-2530","authenticated-orcid":false,"given":"Mariana Gon\u00e7alves","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Department 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