Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release

Yoshinaga, Ryohei; Kawai, Yuko; Oka, Michiko; Fuchikami, Chiaki; Oyama, Tatsuya

doi:10.1016/j.ejphar.2015.01.050

Cited by 15 publications

(15 citation statements)

References 24 publications

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“…From the above results, we inferred that nicotine‐induced reduction of bladder blood flow might be a factor in the deterioration of bladder storage functions. Thus, the following experiments determined if tadalafil, a phosphodiesterase type 5 inhibitor that increases blood flow to the lower urinary tract, could ameliorate the loss of bladder storage functions that followed 13 days of nicotine treatment. Tadalafil was given during the last 6 days of nicotine treatment, and cystometry was performed 1 day after intravesicular instillation with 0.08% acetic acid.…”

Section: Resultsmentioning

confidence: 99%

“…We sought to determine if reversal of the nicotine‐induced reduction of blood flow to the bladder could restore the loss of storage functions and the associated urothelial cell markers. Therefore, for the final 6 days of the nicotine‐treatment, we injected tadalafil, a phosphodiesterase type 5 inhibitor that improves blood flow to the lower urinary tract . The tadalafil treatment not only increased bladder blood flow, but it also improved the bladder storage functions, increased the urothelial expression of UPIII and AQP3, and decreased the expression of HIF1α.…”

Section: Discussionmentioning

confidence: 99%

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Nicotine‐induced hypoxia in rat urothelium deteriorates bladder storage functions

Nagai

Imamura

Ogawa

et al. 2019

Neurourology and Urodynamics

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nicotine‐induced hypoxia in rat urothelium deteriorates bladder storage functions

Nagai

Imamura

Ogawa

et al. 2019

Neurourology and Urodynamics

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“…In rats, repeated administration of tadalafil significantly suppresses the increased contractile responses and smooth muscle actin and collagen levels caused by chronic pelvic ischemia, and has a protective effect on the prostate . Acute and chronic treatment with tadalafil has been shown to improve prostate hypoxia in spontaneous hypertensive rats and prostate blood flow in a rat model of clamping/release of the abdominal aorta . Therefore, the clinical observation of improvement of prostatitis may be due to the reduction of pelvic pain via the inhibition of afferent activity in addition to functional improvement via an increase in pelvic blood perfusion in the lower urinary tract, including the penis, prostate, and bladder, by acute and chronic tadalafil treatment.…”

Section: Discussionmentioning

confidence: 99%

Chronic pelvic pain and prostate inflammation in rat experimental autoimmune prostatitis: Effect of a single treatment with phosphodiesterase 5 inhibitors on chronic pelvic pain

et al. 2018

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“…The PDE5 inhibitor tadalafil augmented SNP‐induced vasodilation in human vesicular‐deferential artery rings . Tadalafil improved the decrease in bladder and prostate blood flow induced by ischemia reperfusion in a time‐dependent manner in rat bladder overdistension emptying and clamping release models . Acute administration of the PDE5 inhibitor, valdenafil, restored hypoxia and caused relaxation in the bladder from a spontaneously hypertensive rat .…”

Section: Pde5 and Vascular Functionmentioning

confidence: 98%

“…135 Tadalafil improved the decrease in bladder and prostate blood flow induced by ischemia reperfusion in a time-dependent manner in rat bladder overdistension emptying and clamping release models. 136 Acute administration of the PDE5 inhibitor, valdenafil, restored hypoxia and caused relaxation in the bladder from a spontaneously hypertensive rat. 137 In an obstructed bladder of a guinea pig, the PDE5 inhibitor sildenafil improved the loss of bladder function accompanied by a significant decrease in blood oxygen saturation through an increase in bladder blood flow.…”

Section: Pde5 and Vascular Functionmentioning

confidence: 99%

Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide–phosphodiesterase type 5–cyclic guanosine 3′,5′‐monophosphate pathway

Higashi

2017

Int J of Urology

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It is well known that there is an association of lower urinary tract symptoms/ benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy. Both lower urinary tract symptoms/benign prostatic hypertrophy and vascular dysfunction have cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes mellitus, aging, obesity and smoking. Inactivation of the phosphodiesterase type 5-cyclic guanosine 3 0 ,5 0 -monophosphate-nitric oxide pathway causes lower urinary tract symptoms/benign prostatic hypertrophy through an enhancement of sympathetic nervous activity, endothelial dysfunction, increase in Rho-associated kinase activity and vasoconstriction, and decrease in blood flow of pelvic viscera. Both endogenous nitric oxide and exogenous nitric oxide act as vasodilators on vascular smooth muscle cells through an increase in the content of cyclic guanosine 3 0 ,5 0 -monophosphate, which is inactivated by phosphodiesterase type 5. In a clinical setting, phosphodiesterase type 5 inhibitors are widely used in patients with lower urinary tract symptoms/benign prostatic hypertrophy. Phosphodiesterase type 5 inhibitors might have beneficial effects on vascular function through not only inhibition of cyclic guanosine 3 0 ,5 0 -monophosphate degradation, but also increases in testosterone levels and nitric oxide bioavailability, increase in the number and improvement of the function of endothelial progenitor cells, and decrease in insulin resistance. In the present review, the relationships between lower urinary tract symptoms/benign prostatic hypertrophy, the phosphodiesterase type 5-nitric oxidecyclic guanosine 3 0 ,5 0 -monophosphate pathway, vascular function and cardiovascular outcomes are examined.Key words: benign prostatic hypertrophy, lower urinary tract symptoms, nitric oxide, phosphodiesterase type 5-cyclic guanosine 3 0 ,5 0 -monophosphate, vascular function.

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Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release

Cited by 15 publications

References 24 publications

Nicotine‐induced hypoxia in rat urothelium deteriorates bladder storage functions

Nicotine‐induced hypoxia in rat urothelium deteriorates bladder storage functions

Chronic pelvic pain and prostate inflammation in rat experimental autoimmune prostatitis: Effect of a single treatment with phosphodiesterase 5 inhibitors on chronic pelvic pain

Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide–phosphodiesterase type 5–cyclic guanosine 3′,5′‐monophosphate pathway

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