8 4 1What ' s known on the subject? and What does the study add? Angiotensin II is the main effector peptide in the bladder local renin-angiotensin system. This experiment demonstrates the role of this local renin-angiotensin system with respect to bladder outlet obstruction. OBJECTIVE• To determine if treatment with an angiotensin II type 1 (AT-1) receptor antagonist, losartan, can prevent the structural and functional changes that occur in a mouse model of bladder outlet obstruction (BOO).
MATERIALS AND METHODS• Twenty-four Balb/CAN mice underwent partial urethral obstruction for 6 weeks.• Twelve mice were given oral losartan (10 mg/kg/day), and 12 were not. Six mice served as unobstructed controls, and six unobstructed mice were given oral losartan (10 mg/kg/day) to determine the effect of angiotensin II inhibition on the normal bladder.• Bladder capacity (C), detrusor pressure during voiding (Pdet) and volume at fi rst non-voiding contraction (NVC1) as a percentage of C were recorded after 6 weeks.• Bladders were stained with haematoxylin and eosin for measurement of detrusor muscular thickness, and graded as 1 = atrophy ( < 100 μ m thick), 2 = normal (100 -200 μ m thick), 3 = hypertrophy ( > 200 μ m thick) compared with controls.
RESULTS• Compared with controls, BOO mice had greater C (153.5 ± 20.9 vs 57.5 ± 7.4 μ l, P < 0.01), higher Pdet (28.8 ± 2.1 vs 12.1 ± 2.1 mm Hg), lower NVC1 (median = 24% vs 54% P = 0.03). BOO mice manifested greater bladder weight (93.2 ± 11.7 mg vs 26.8 ± 2.40 mg, P < 0.01) and greater detrusor muscle thickness (median 3 vs 2, P = 0.02).• Compared with untreated BOO mice, mice treated with losartan had greater mean C (248.8 ± 28.6 vs 153.5 ± 20.9 μ L, P = 0.01), no signifi cant change in mean Pdet (24.7 ± 1.6 vs 28.8 ± 2.1 mm Hg, P = 0.2) and a higher mean NVC1 (47% vs 24%, P = 0.02).• Treatment with losartan mediated an insignifi cant reduction in mean bladder weight (68.1 ± 9.1 mg vs 93.2 ± 11.7 mg, P = 0.10), but a signifi cant reduction in detrusor muscle thickness (median 2 vs 3, P = 0.02). Losartan did not mediate any signifi cant structural or functional changes in the unobstructed mouse bladder.
CONCLUSION• In a mouse model of BOO, treatment with an AT-1 antagonist partially prevented the urodynamic and structural changes that otherwise occur with BOO.
KEYWORDSangiotensin II , bladder outlet obstruction , benign prostatic enlargement , detrusor overactivity , detrusor hypertrophy Study Type -Therapy (case control) Level of Evidence 3b
