Involvement of angiotensin II type 1 receptor on pathological remodeling and dysfunction in obstructed bladder.
OBJECTIVE
To determine whether long-term administration of an angiotensin II type 1 receptor antagonist improves morphology and function in obstructed bladders.


METHODS
Male Sprague-Dawley rats underwent surgery to produce bladder outlet obstruction (bladder outlet obstruction group; n = 32) or sham surgery (sham group; n = 16). A total of 2 weeks later, 16 bladder outlet obstruction-rats were given the AT1 antagonist, candesartan, subcutaneously (candesartan group) using an osmotic pump for 4 weeks; the remaining bladder outlet obstruction-rats received vehicle (bladder outlet obstruction group). A total of 6 weeks after surgery, we compared continuous cystometry, bladder weight, strip contraction, histology and messenger ribonucleic acid expression of growth factors, nicotinamide adenine dinucleotide phosphate oxidase 1 and renin-angiotensin system components among the three groups.


RESULTS
Bladder weights markedly increased with bladder outlet obstruction (578 ± 159 mg), and candesartan (344 ± 111 mg) suppressed this increase. Micturition pressure, which was significantly higher with bladder outlet obstruction, was unaffected by candesartan. The shortened micturition interval and decreased micturition volume with bladder outlet obstruction were significantly prolonged and increased by candesartan. Candesartan also significantly decreased residual urine. Histologically, the collagen fiber-to-muscle ratio was significantly increased with bladder outlet obstruction (0.85 ± 0.25) compared with the sham group (0.53 ± 0.18); this increase was suppressed by candesartan (0.49 ± 0.21). The messenger ribonucleic acid expression of heparin-binding epidermal growth factor-like growth factor, transforming growth factor-β1 and nicotinamide adenine dinucleotide phosphate oxidase 1 significantly increased with bladder outlet obstruction, but it was significantly reduced by candesartan. Compared with the bladder outlet obstruction group, candesartan increased the maximal contraction of bladder strips for all stimuli except for angiotensin II.


CONCLUSIONS
These findings suggest that bladder angiotensin II type 1 receptors contribute to the pathophysiology of remodeling and dysfunction in obstructed bladder.
Department of Urology, Fukushima Medical University, Fukushima, Japan. kaika@fmu.ac.jp
Ken
K
Aikawa
Takio
T
Sakai
Kei
K
Ishibashi
Homare
H
Shiomi
Koji
K
Sagawa
Shin
S
Kumagai
Masao
M
Kataoka
Hidenori
H
Akaihata
Osamu
O
Yamaguchi
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D008297:Male; D010919:Placebos; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014563:Urodynamics / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010919:Placebos; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C081643:candesartan