Endothelin-1 and urinary bladder hyperplasia following partial bladder outlet obstruction.
Urinary bladder hypertrophy and hyperplasia is a common feature of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1). ET-1 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 [endothelin-A and -B (ET(A) and ET(B))] in bladder vascular smooth muscle cells (SMC) proliferation. In the presence of 3-week-old BOO serum, ET(A) and ET(B) antagonists 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 ET(A) and ET(B) antagonists, respectively) and bladder neck (p = 0.01 for both ET(A) and ET(B) antagonists). These results suggest that ET-1 antagonists may prevent SMC hyperplasia associated with partial BOO.
Khan
M A
MA
Department of Urology, Royal Free and University College Medical School, University College London, UK. ktasmas@aol.com
Shukla
N
N
Thompson
C S
CS
Mumtaz
F H
FH
Mikhailidis
D P
DP
Morgan
R J
RJ
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D019332:Endothelin-1 / Q000502:physiology*; D006965:Hyperplasia; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D001743:Urinary Bladder / Q000473:pathology*; D001748:Urinary Bladder Neck Obstruction / Q000473:pathology*
D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; C086539:BQ 788; D001973:Bromodeoxyuridine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)