Tadalafil Ameliorates Chronic Ischemia-Associated Bladder Overactivity in Fructose-Fed Rats by Exerting Pelvic Angiogenesis and Enhancing p-eNOS Expression
Year: 2025
Type: article
Abstract: Metabolic syndrome (MetS) can contribute to a chronic ischemia-relative overactive bladder (OAB). Using fructose-fed rats (FFRs), a rat model of MetS, we investigated the effects of tadalafil (a phosphodiesterase-5 inhibitor) on MetS-associated chronic bladder ischemia and bladder overactivity. Phenotypes of the OAB, including increased micturition frequency and a shortened intercontractile interval in cystometry, were observed in FFRs, together with reduced bladder blood perfusion (in empty bladders) via laser color Doppler imaging and elevated serum nitrite levels, suggesting chronic ischemia-related bladder dysfunction. Treatment with tadalafil (2 mg/kg) promoted pelvic angiogenesis, as shown by magnetic resonance imaging, and increased VEGF and p-eNOS overexpression in the bladder. This treatment restored bladder perfusion and alleviated bladder overactivity without significantly altering most MetS parameters. At the molecular level, FFRs exhibited increased ischemia markers (NGF, HIF-2α, and AMPK-α2) and decreased p-AMPK-α2, along with elevated proinflammatory mediators (ICAM-1, nuclear NF-κB, COX-2, IL-1β, IL-6, and TNF-α), enhanced mitochondria biogenesis (PGC-1α, TFAM, and mitochondria DNA copy number), oxidative stress (decreased nuclear NRF2, increase MnSOD and 8-OHdG staining), and tissue fibrosis (increased TGF-β1, collagen I, and fibronectin). Tadalafil treatment improved these effects. Together, these findings suggest that tadalafil may promote VEGF-associated angiogenesis, enhance p-eNOS staining in the bladder vasculature, normalize bladder perfusion in microcirculation, and reduce serum nitrite levels. Consequently, tadalafil mitigates the adverse effects of chronic ischemia/hypoxia, improving bladder overactivity. We elucidated the mechanisms underlying the tadalafil-mediated amelioration of MetS-associated OAB symptoms.
DOI: 10.3390/ijms26031363
Authors: Wei-Chia Lee, Steve Lu, Chia-Hao Su, You-Lin Tain, Kay L. H. Wu, Chien-Ning Hsu, Hong-Tai Tzeng
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G1125870951, G1938408789, The Role of Chronic Bladder Ischemia in Metabolic Syndrome-Associated Bladder Overactivity of Fructose-Fed Rats: Focusing on Pathophysiology and Treatment Strategies., G3040754987, Using the Fructose-Fed Rat Model to Explore the Pathophysiology and Treatment Strategy of Metabolic Syndrome-Associated Bladder Overactivity: Focusing on the Short-Chain Fatty Acid and Associated Gut Microbiota., G4470233115, G4494135322, G6277552470, G6480032417, G7243232451, G7918613341
OpenAlex ID: W4407227012