Down-regulation of endothelin-B receptor sites in cavernosal tissue of a rabbit model of partial bladder outlet obstruction: potential clinical relevance.
Erectile dysfunction (ED) is a common problem that significantly affects quality of life and psychological well-being. Benign prostatic hyperplasia (BPH) is the commonest known benign proliferative disorder. Recently there has been growing evidence to suggest that patients with high BPH symptom scores have an increased incidence of ED. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that is thought to play an important role as a modulator of erectile physiology and dysfunction. We investigated whether there were any changes in the penile histology and in the density and distribution of ET-1 and its receptor subtypes in the corpora cavernosa of a rabbit model of partial bladder outflow obstruction (BOO). BOO was induced in 12 adult New Zealand White rabbits; 12 sham-operated rabbits acted as controls. Penises were excised after 3 and 6 weeks (n=6 each for control and BOO). Low- and high-resolution autoradiography was performed using radioligands for ET-1, ET(A) and ET(B) receptors and the results were analysed densitometrically. Ultrastructural evaluation of the corpus cavernosum (CC) was also performed. ET-1, ET(A) and ET(B) receptor-binding sites were primarily localised to the smooth-muscle cells (SMC) of the CC and to the endothelium lining the cavernosal space. ET(B) receptor-binding sites were significantly decreased (P=0.04) in the 6-week BOO cavernosal tissue. These receptor changes were accompanied by ultrastructural changes in the CC. ET-1 may play a role in the pathophysiology of ED associated with BPH. This may partly be due to enhanced vasoconstrictor actions and SMC proliferation secondary to a reduction in ET(B) receptors. Further work is needed to evaluate this possibility.
Khan
M A
MA
Department of Urology, Royal Free Hospital, Royal Free and University College Medical School, Royal Free Campus, Pond Street, London NW3 2QG, UK.
Dashwood
M R
MR
Thompson
C S
CS
Auld
J
J
Morgan
R J
RJ
Mikhailidis
D P
DP
D000199:Actins / Q000032:analysis; D000818:Animals; D001345:Autoradiography; D001786:Blood Glucose; D001806:Blood Urea Nitrogen; D015536:Down-Regulation / Q000502:physiology*; D004573:Electrolytes / Q000097:blood; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010413:Penis / Q000737:chemistry / Q000648:ultrastructure; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011817:Rabbits; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000032:analysis / Q000378:metabolism*; D001743:Urinary Bladder / Q000737:chemistry / Q000503:physiopathology / Q000648:ultrastructure; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism*
D000199:Actins; D001786:Blood Glucose; D004573:Electrolytes; D019332:Endothelin-1; D007457:Iodine Radioisotopes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin