Long‐term tadalafil administration can prevent functional and structural changes of the urinary bladder in male rats with partial bladder outlet obstruction

Abstract

Aims There have been few reports on whether long‐term oral phosphodiesterase 5 inhibitor administration can ameliorate bladder changes due to bladder outlet obstruction (BOO). Therefore, we clarified the chronological changes of the bladder using male BOO rats and evaluated the effects of tadalafil on these changes. Methods Eight‐week‐old male Sprague‐Dawley rats were used. BOO was created by placing a polyethylene catheter around the urethra. Then, the rats were orally treated with a vehicle, or tadalafil 2 or 10 mg/kg until each evaluation period. Cystometric measurements were performed and the degree of fibrosis in the smooth muscle layer was evaluated at 2, 4, and 16 weeks. Results In BOO rats, a significant increase in the number of non‐voiding contractions (NVCs) and a shortened intercontraction interval (ICI) were observed in the earlier phase (2 and 4 weeks) compared to Sham rats. In the chronic phase (16 weeks), markedly increased residual urine volume and an extended ICI were observed accompanied by enhanced smooth muscle fibrosis. These results indicated that the bladder in BOO rats represented the overactive phenotype in the earlier phase and changed into the underactive phenotype in the chronic phase. Even in Sham rats, an increased number of NVCs and enhanced fibrosis were observed with time. Tadalafil administration significantly prevented these bladder changes in both BOO and Sham rats. Conclusions Long‐term oral administration of tadalafil can prevent functional and histological changes in the BOO rat bladder. This agent is also effective for the bladder functional change even in non‐obstructed rats.

Co-administration of sodium hydrosulfide and tadalafil modulates hypoxia and oxidative stress on bladder dysfunction in a rat model of bladder outlet obstruction

“…In the present study, urethral ligation reduced in vitro contraction responses in detrusor smooth muscle to carbachol, EFS, ATP and KCl. Furthermore, in the current study, tadalafil treatment partially prevented reduced contractile responses in the obstructed bladder, similar to an earlier study (3). On the other hand, decreased contractility of isolated bladder strips was considerably potentiated by NaHS alone.…”

“…NO has a crucial physiological role in the proliferation and differentiation of several cell types and can act as a neurotransmitter in the urothelium and affect bladder function (3,26). However, the relation between the expression levels of NOS isoforms in bladder function remains unclear.…”

“…Tadala-fil is the only phosphodiesterase type-5 inhibitor (PDE5i) approved for treating moderate to severe LUTS/BPH (2). A previous study showed that tadalafil improved blood flow of the bladder as well as functional and histological alterations in the partial BOO (PBOO) rat bladder (3).…”

A constrained mixture-micturition-growth (CMMG) model of the urinary bladder: Application to partial bladder outlet obstruction (BOO)

“…Motivated by the application to BPH, this project used male rats to produce the BOO condition underlying male LUTS ( Zvara et al, 2002 ). A recent study also reported that this male BOO model exhibits the early hypertrophy-compensation phase followed by the later decompensation phase of bladder dysfunction, similar to those observed in human BPH/BOO ( Shinkai et al, 2020 ).…”