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SAMPLE ABSTRACT: The sample shown below is a model for the type of abstract requested. Please follow style and text structure. THE
ROLE OF ANGIOTENSIN II IN STRESS URINARY INCONTINENCE – A RAT MODEL Purpose: Stress urinary incontinence (SUI) affects nearly 30 million American women. 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. Our group recently identified the presence of Ang-II receptors in the rodent prostatic urethra, but a functional role for Ang-II in sphincteric function has not yet been elucidated. We investigate the role of Ang-II in urethral tone in a rat model of SUI. Materials and Methods: Abdominal leak point pressure (ALPP) and retrograde urethral pressure profilometry (RLPP) were measured in 70 female virgin female Sprague Dawley rats (Harlan Sprague Dawley, Indianapolis, IN) weighing 200-300 grams. 30 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 (50mg/kg), Angiotensin Type 2 (AT-2) receptor antagonist (10mg/kg), or Ang-II (2mg/kg). Mean arterial pressure (MAP) was measured at baseline, following 7 days of AT-1 inhibitor, during AT-2 inhibition, and during Ang-II administration (n=3 for each). Results: In non-operated rats, 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?11.7 mmHg, to 13.5?5.7 and 31.0?7.2 mmHg, respectively (p< 0.01). Following urethrolysis, RLPP and ALPP decreased from 21.4?2.0 and 39.2?3.3 mmHg, to 13.1?1.5 and 21.6?1.9 mmHg, respectively (p<0.01). After pudendal nerve transection, 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). Following surgery, Ang-II administration restored RLPP and ALPP to baseline pre-surgical values. Overall, mean MAP at baseline (all 9 rats) was 137 mm Hg (range 132 - 141). In the 3 rats receiving AT-1 inhibitor, MAP decreased to 73 mm Hg (range 66 - 79). AT-2 administration did not initially affect MAP from baseline values, but after 4 minutes a rise in MAP to 180 mm Hg (range 176-185) was observed. Ang-II administration resulted in an immediate increase in MAP to 186 mm Hg (range 182 - 189) 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. Urethral smooth muscle effects appear to be independent of changes in blood pressure and blood flow. Ang-II appears to serve a functional role in the maintenance of urethral tone and stress continence. |