Effect of angiotensin II receptor antagonist telmisartan on detrusor overactivity in rats with bladder outlet obstruction.
OBJECTIVE
To investigate the changes of expression in both the nerve growth factor (NGF) and the angiotensin II type 1 (AT1) receptors in the urothelium and the detrusor muscle in a rat model of bladder outlet obstruction (BOO). To determine whether the AT1 receptor antagonist telmisartan alleviated the detrusor overactivity in rats with BOO.


METHODS
Male Sprague-Dawley rats were randomly assigned to 3 groups. The control group (n = 10) was sham-operated. The animals in the BOO (n = 20) and the telmisartan groups (n = 20) underwent a partial BOO operation. The telmisartan group received telmisartan (3 mg/kg/d) for 14 days. Cystometry was performed in all 3 groups for 2 weeks after surgery. The expression levels and the cellular distribution of NGF and AT1 receptors were quantified by Western blot analysis and immunofluorescence staining.


RESULTS
On cystometry, the intercontraction interval was shorter and the mean number of nonvoiding contractions was increased in the BOO group, compared with those in the control group. The intercontraction interval was longer and the number of nonvoiding contractions was reduced in the telmisartan group, compared with those in the BOO group. In Western blotting and immunofluorescence staining, we found that the expression and the immunoreactivity of NGF and the AT1 receptors were increased in the BOO group, compared with those in the control group. However, with oral administration of telmisartan, those of NGF and AT1 were decreased.


CONCLUSIONS
The AT1 receptors may play a significant role in the pathogenesis of the detrusor overactivity in a rat model of BOO.
Department of Urology, College of Medicine, Hallym University, Seoul, Korea.
Sung Tae
ST
Cho
Eun Young
EY
Park
Joon Chul
JC
Kim
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D000077333:Telmisartan; D001748:Urinary Bladder Neck Obstruction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D044140:Receptor, Angiotensin, Type 1; D020932:Nerve Growth Factor; D000077333:Telmisartan