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Both MetS and ovarian hormone deficiency (OHD) are linked to bladder overactivity. Nitric oxide (NO) is known to reduce inflammation and promote healing but its effect on bladder overactivity in MetS and OHD is unclear. This study aimed to investigate NO\u2019s impact on detrusor muscle hyperactivity in rats with MetS and OHD. Female Sprague-Dawley rats were divided into seven groups based on diet and treatments involving L-arginine (NO precursor) and L-NAME (NOS inhibitor). After 12 months on a high-fat, high-sugar diet with or without OVX, a cystometrogram and tracing analysis of voiding behavior were used to identify the symptoms of detrusor hyperactivity. The MetS with or without OHD group had a worse bladder contractile response while L-arginine ameliorated bladder contractile function. In summary, MetS with or without OHD decreased NO production, reduced angiogenesis, and enhanced oxidative stress to cause bladder overactivity, mediated through the NF-kB signaling pathway, whereas L-arginine ameliorated the symptoms of detrusor overactivity and lessened oxidative damage via the NRF2\/HIF-1\u03b1 signaling pathway in MetS with or without OHD-induced OAB.<\/jats:p>","DOI":"10.3390\/ijms252011103","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T07:58:32Z","timestamp":1729065512000},"page":"11103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of Nitric Oxide on Bladder Detrusor Overactivity through the NRF2 and HIF-1\u03b1 Pathways: A Rat Model Induced by Metabolic Syndrome and Ovarian Hormone Deficiency"],"prefix":"10.3390","volume":"25","author":[{"given":"Hung-Yu","family":"Lin","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine, I-Shou University, Kaohsiung 84001, Taiwan"},{"name":"Division of Urology, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824005, Taiwan"},{"name":"Division of Urology, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-He","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Agricultural, Forestry, Fishery, Livestock and Aquaculture Carbon Emission Inventory and Emerging Compounds, General Research Service Center, National Pingtung University of Science and Technology, Pingtung County 912301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Jyh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Parasitology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-9311","authenticated-orcid":false,"given":"Kuang-Shun","family":"Chueh","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80661, Taiwan"},{"name":"Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-Jui","family":"Juan","sequence":"additional","affiliation":[{"name":"Kaohsiung Armed Forces General Hospital, Kaohsiung 802301, Taiwan"},{"name":"Department of Thoracic Surgery Division, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Wen","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-095X","authenticated-orcid":false,"given":"Yi-Chen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Mien","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chen","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0607-9093","authenticated-orcid":false,"given":"Yung-Shun","family":"Juan","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S","article-title":"Definition, diagnosis and classification of diabetes mellitus and its complications. 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