Possible role of endothelin-1 in the rabbit urinary bladder hyperplasia secondary to partial bladder outlet obstruction.
OBJECTIVE
Urinary bladder hypertrophy and hyperplasia are common features of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1), which is a potent vasoconstrictor peptide with mitogenic properties. Using an animal model of partial BOO, we investigated the potential role of ET-1 and its receptor subtypes (ET(A) and ET(B)) in bladder smooth muscle cell (SMC) proliferation.


METHODS
Partial BOO 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 using standard explant methodology. At passage 2, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or partial BOO serum (BRS) in the presence or absence of ET(A)-antagonist (BQ123) or ET(B)-antagonist (BQ788). SMC proliferation was then measured 24 h later with 5-bromo-2'deoxy-uracil and by cell counting using a haemocytometer at 48 h. Immunostaining for alpha-actin was performed on detrusor and bladder neck cells to confirm the presence of smooth muscle cells.


RESULTS
BQ123 and BQ788 did not influence detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of BRS, BQ123 and BQ788 (100 nmol/L) significantly (p = 0.008) inhibited detrusor and bladder neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with BQ123 and BQ788, respectively) and bladder neck (p = 0.01 for both BQ123 and BQ78).


CONCLUSIONS
These results suggest that ET antagonists may have a role in preventing SMC hyperplasia associated with partial BOO.
Khan
M A
MA
Department of Urology, Royal Free and University College Medical School, University College London, UK.
Shukla
N
N
Auld
J
J
Thompson
C S
CS
Mumtaz
F H
FH
Stansby
G P
GP
Morgan
R J
RJ
Mikhailidis
D P
DP
D000818:Animals; D002455:Cell Division / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology*; D006965:Hyperplasia; D006984:Hypertrophy; D008297:Male; D011817:Rabbits; D017466:Receptors, Endothelin / Q000502:physiology; D001743:Urinary Bladder / Q000473:pathology*; D001748:Urinary Bladder Neck Obstruction / Q000473:pathology*
D019332:Endothelin-1; D017466:Receptors, Endothelin