Possible role of endothelin-1 in the rabbit urinary bladder hyperplasia secondary to partial bladder outlet obstruction

Objectives: Urinary bladder hypertrophy and hyperplasia are common features of bladder outlet obstruction (BOO). The urinary bladder is known to synth esize endothelin-1 (ET-1), which is a potent vasoconstrictor peptide with m itogenic properties. Using an animal model of partial BOO, we investigated the potential role of ET-1 and its receptor subtypes (ETA and ETB) in bladd er smooth muscle cell (SMC) proliferation. Materials and methods. Partial B OO was produced in adult male New Zealand White rabbits. After 3 weeks, the bladder was removed and SMCs from the dome and bladder neck were grown usi ng standard explant methodology. At passage 2, the cells were made quiescen t and then further incubated in foetal calf serum (FCS), control age-matche d rabbit serum (CRS) or partial BOO serum (BRS) in the presence or absence of ETA-antagonist (BQ123) or ETB-antagonist (BQ788). SMC proliferation was then measured 24 h later with 5-bromo-2'deoxy-uracil and by cell counting u sing a haemocytometer at 48 h. Immunostaining for alpha-actin was performed on detrusor and bladder neck cells to confirm the presence of smooth muscl e cells. Results: BQ123 and BQ788 did not influence detrusor or bladder nec k SMC proliferation in FCS or CRS. However, in the presence of BRS, BQ123 a nd BQ788 (100 nmol/L) significantly (p = 0.008) inhibited detrusor and blad der neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with BQ123 and BQ788, respectively) and bladd er neck (p = 0.01 for both BQ123 and BQ78). Conclusions: These results sugg est that ET antagonists may have a role in preventing SMC hyperplasia assoc iated with partial BOO.