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Nicotine‐induced hypoxia in rat urothelium deteriorates bladder storage functions
Author(s) -
Nagai Takashi,
Imamura Tetsuya,
Ogawa Teruyuki,
Minagawa Tomonori,
Domen Takahisa,
Suzuki Toshiro,
Ueno Manabu,
Ishizuka Osamu
Publication year - 2019
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.24050
Subject(s) - nicotine , medicine , urination , cystometry , urothelium , urinary system , endocrinology , urology , blood flow , urinary bladder , hypoxia (environmental) , anesthesia , chemistry , organic chemistry , oxygen
Aims To measure the effects of nicotine on lower urinary tract symptoms (LUTS), bladder blood flow, and the urothelial markers hypoxia‐inducible factor 1α (HIF1α), uroplakin III (UPIII), and aquaporin 3 (AQP3). Methods Ten‐week‐old female Sprague Dawley rats were subcutaneously injected with 2 mg/kg nicotine (n = 17) or vehicle (control, n = 18) twice daily for 13 days. Some nicotine‐treated rats (n = 10) were injected daily with 1 mg/kg tadalafil for the last 6 days of nicotine treatment. One day before cystometry, the bladders of some nicotine‐treated 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 HIF1α, UPIII, and AQP3. Results Following acetic acid treatment, both voiding interval and micturition volume of the nicotine‐treated rats were significantly lower than controls. Nicotine‐treated rats had lower blood flow than controls, and the urothelial expression of HIF1α was higher than controls. Simultaneously, the expressions of UPIII and AQP3 were decreased. Tadalafil treatment increased bladder blood flow, and nicotine‐treated rats had increased voiding interval and micturition volume. Further, the expression of HIF1α decreased, and both UPIII and AQP3 levels increased. Conclusions Nicotine‐treated rats stimulated by intravesicular acetic acid instillation exhibited deterioration of bladder storage functions. Changes in tissue markers in the nicotine‐treated 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.