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The role of angiotensin II in stress urinary incontinence: A rat model
Author(s) -
Phull Hardeep,
Salkini Mohamad,
Escobar Christina,
Purves Todd,
Comiter Craig V.
Publication year - 2007
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20339
Subject(s) - medicine , urology , urinary incontinence , angiotensin ii , endocrinology , receptor
Aims Pharmacological treatment for stress urinary incontinence (SUI) is limited to the use of non‐selective alpha‐agonists, which are often ineffective. Non‐adrenergic mechanisms have also been implicated in urethral closure, including angiotensin II (Ang‐II), which has been demonstrated throughout the urinary tract. We investigate the role of Ang‐II in urethral tone in a rat model of SUI. Methods Abdominal leak point pressure (ALPP) and retrograde urethral pressure profilometry (RLPP) were measured in 70 female virgin rats. Thirty rats underwent pudendal nerve injury (PNT), 30 had circumferential urethrolysis (U‐Lys), and 10 had sham surgery. Rats received daily doses of Angiotensin Type 1 (AT‐1) receptor inhibitor (20 mg/kg), Angiotensin Type 2 (AT‐2) receptor antagonist (10 mg/kg), or Ang‐II (2 mg/kg). Results Following U‐Lys, RLPP and ALPP decreased from 21.4 ± 2.0 and 39.2 ± 3.3 mm Hg, to 13.1 ± 1.5 and 21.6 ± 1.9 mmHg, respectively ( P <0.01). After PNT, RLPP, and ALPP decreased from 21.0 ± 1.6 and 41.9 ± 3.0 mmHg to 13.1 ± 1.5 and 24.7 ± 3.3 mmHg, respectively ( P <0.01). AT‐1 inhibitor caused significant decrease in RLPP and ALPP from 21.0 ± 6.2 and 41.8 ± 9.4 mmHg, to 12.0 ± 3.8 and 25.6 ± 6.6 mmHg, respectively ( P <0.01). Likewise, AT‐2 treatment reduced RLPP and ALPP from 21.4 ± 6.3 and 40.1 ± 1.7 mmHg, to 13.5 ± 5.7 and 31.0 ± 7.2 mmHg, respectively ( P <0.01). Following surgery, Ang‐II administration restored RLPP and ALPP to baseline presurgical values. Conclusions AT‐1 and AT‐2 receptor inhibition significantly lowers urethral resistance, comparable to either neurogenic or urethrolytic injury. Ang‐II treatment restored urethral tone in rats with intrinsic sphincter dysfunction. Ang II appears to serve a functional role in the maintenance of urethral tone and stress continence. Neurourol. Urodynam. © 2006 Wiley‐Liss, Inc.