The role of angiotensin II in stress urinary incontinence: A rat model

Abstract

Aims: Pharmacological treatment for stress urinary incontinence (SUI) is limited to the use of nonselective alpha-agonists, which are often ine¡ective. 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 pro¢lome-try (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 AE 2.0 and 39.2 AE 3.3 mm Hg, to 13.1 AE1.5 and 21.6 AE 1.9 mmHg, respectively (P<0.01). After PNT, RLPP, and ALPP decreased from 21.0 AE 1.6 and 41.9 AE 3.0 mmHg to 13.1 AE1.5 and 24.7 AE 3.3 mmHg, respectively (P<0.01). AT-1 inhibitor caused signi¢cant decrease in RLPP and ALPP from 21.0 AE 6.2 and 41.8 AE 9.4 mmHg, to 12.0 AE 3.8 and 25.6 AE 6.6 mmHg, respectively (P<0.01). Likewise, AT-2 treatment reduced RLPP and ALPP from 21.4 AE 6.3 and 40.1 AE1.7 mmHg, to 13.5 AE 5.7 and 31.0 AE 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 signi¢cantly 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.

The angiotensin II receptors type 1 blockage affects the urinary bladder activity in hyperosmolar-induced detrusor overactivity in rats: Preliminary results

“…1 NCNA mechanisms implicated in the urethral sphincter action have been described previously. Phull et al 2 observed that the blockade of angiotensin II receptors type 1 (AT1) and type 2 (AT2) decreases urethral resistance in stress urinary incontinence rat model. Moreover, angiotensin II treatment improves urethral tone in sphincter deficiency in the rat model.…”

Pharmacological Modulation of Mucosa-Related Impairment of β-Adrenoceptor-Mediated Relaxation in Human Detrusor

“…The lower urinary tract harbors a local renin-angiotensin system [30] that contributes to stress incontinence in animal models [31]. A post hoc analysis of antihypertensive patients treated with AT 1 receptor blockers revealed lesser lower urinary tract symptoms than the untreated subjects [32].…”

Development of a rabbit's urethral sphincter deficiency animal model for anatomical-functional evaluation

“…One of the most used methods to evaluate urethral resistance in rats is the determination of LPP (11). In these animal models, the intravesical pressure can be evaluated by urethral or suprapubic catheter (12,13). However, to determine the LPP in rats requires a very well trained investigator to eliminate confounding variables, especially because the LPP evaluation can trigger micturition and urethral catheter may increase the urethral resistance (14).…”