1. Effects of Nitric Oxide on Bladder Detrusor Overactivity through the NRF2 and HIF-1α Pathways: A Rat Model Induced by Metabolic Syndrome and Ovarian Hormone Deficiency.
- Author
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Lin HY, Lu JH, Lin RJ, Chueh KS, Juan TJ, Mao JW, Lee YC, Chuang SM, Shen MC, Sun TW, and Juan YS
- Subjects
- Animals, Female, Rats, Arginine pharmacology, Nitric Oxide metabolism, Urinary Bladder, Overactive metabolism, Urinary Bladder, Overactive etiology, Urinary Bladder, Overactive drug therapy, Urinary Bladder, Overactive physiopathology, NF-E2-Related Factor 2 metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Metabolic Syndrome metabolism, Rats, Sprague-Dawley, Disease Models, Animal, Signal Transduction drug effects, Urinary Bladder metabolism, Urinary Bladder drug effects, Urinary Bladder pathology, Urinary Bladder physiopathology
- Abstract
Metabolic syndrome (MetS) includes cardiovascular risk factors like obesity, dyslipidemia, hypertension, and glucose intolerance, which increase the risk of overactive bladder (OAB), characterized by urgency, frequency, urge incontinence, and nocturia. 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's 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-1α signaling pathway in MetS with or without OHD-induced OAB.
- Published
- 2024
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