{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T13:18:31Z","timestamp":1776604711045,"version":"3.51.2"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"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":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To measure the effects of nicotine on lower urinary tract symptoms (LUTS), bladder blood flow, and the urothelial markers hypoxia\u2010inducible factor 1\u03b1 (HIF1\u03b1), uroplakin III (UPIII), and aquaporin 3 (AQP3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten\u2010week\u2010old female Sprague Dawley rats were subcutaneously injected with 2\u2009mg\/kg nicotine (n\u2009=\u200917) or vehicle (control, n\u2009=\u200918) twice daily for 13 days. Some nicotine\u2010treated rats (n\u2009=\u200910) were injected daily with 1\u2009mg\/kg tadalafil for the last 6 days of nicotine treatment. One day before cystometry, the bladders of some nicotine\u2010treated and control rats were instilled with 0.08% acetic acid. Urinary frequency and volume were measured 1 day after treatment. Blood flow in the bladder neck was measured, and the urothelia were immunochemically assayed for HIF1\u03b1, UPIII, and AQP3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following acetic acid treatment, both voiding interval and micturition volume of the nicotine\u2010treated rats were significantly lower than controls. Nicotine\u2010treated rats had lower blood flow than controls, and the urothelial expression of HIF1\u03b1 was higher than controls. Simultaneously, the expressions of UPIII and AQP3 were decreased. Tadalafil treatment increased bladder blood flow, and nicotine\u2010treated rats had increased voiding interval and micturition volume. Further, the expression of HIF1\u03b1 decreased, and both UPIII and AQP3 levels increased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nicotine\u2010treated rats stimulated by intravesicular acetic acid instillation exhibited deterioration of bladder storage functions. Changes in tissue markers in the nicotine\u2010treated rats were consistent with hypoxia and loss of urothelial function. Restoration of blood flow reversed the nicotine effects. Nicotine may induce LUTS through reduced bladder blood flow and urothelial hypoxia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24050","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T12:45:11Z","timestamp":1560429911000},"page":"1560-1570","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nicotine\u2010induced hypoxia in rat urothelium deteriorates bladder storage functions"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8116-1751","authenticated-orcid":false,"given":"Takashi","family":"Nagai","sequence":"first","affiliation":[{"name":"Department of Urology Shinshu University School of Medicine Matsumoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Urology Shinshu University School of Medicine Matsumoto 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