Angiotensin II type 1 (AT-1) receptor inhibition partially prevents the urodynamic and detrusor changes associated with bladder outlet obstruction: a mouse model

作者：Comiter Craig^*; Phull Hardeep S

来源：BJU International, 2012, 109(12): 1841-1846.

DOI：10.1111/j.1464-410X.2011.10580.x

• angiotensin II
• bladder outlet obstruction
• benign prostatic enlargement
• detrusor overactivity
• detrusor hypertrophy

Study Type Therapy (case control) Level of Evidence 3b What'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 first 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 mu m thick), 2 = normal (100-200 mu m thick), 3 = hypertrophy (>200 mu m thick) compared with controls. RESULTS Compared with controls, BOO mice had greater C (153.5 +/- 20.9 vs 57.5 +/- 7.4 mu 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 mu L, P= 0.01), no significant 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 insignificant reduction in mean bladder weight (68.1 +/- 9.1 mg vs 93.2 +/- 11.7 mg, P= 0.10), but a significant reduction in detrusor muscle thickness (median 2 vs 3, P= 0.02). Losartan did not mediate any significant 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.

• 出版日期2012-6