Phull Hardeep, Salkini Mohamad, Escobar Christina, Purves Todd, Comiter Craig V
Section of Urology, Department of Surgery, University of Arizona Health Sciences Center, Tucson, Arizona, USA.
Neurourol Urodyn. 2007;26(1):81-8; discussion 89. doi: 10.1002/nau.20339.
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.
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).
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.
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.
压力性尿失禁（SUI）的药物治疗仅限于使用非选择性α-激动剂，而这些药物往往无效。非肾上腺素能机制也与尿道闭合有关，包括血管紧张素II（Ang-II），它在整个泌尿道中都有发现。我们在SUI大鼠模型中研究Ang-II在尿道张力中的作用。
对70只未交配的雌性大鼠测量腹压漏尿点压力（ALPP）和逆行尿道压力测定（RLPP）。30只大鼠接受阴部神经损伤（PNT），30只进行环周尿道松解术（U-Lys），10只进行假手术。大鼠每日接受血管紧张素1型（AT-1）受体抑制剂（20mg/kg）、血管紧张素2型（AT-2）受体拮抗剂（10mg/kg）或Ang-II（2mg/kg）的剂量。
U-Lys术后，RLPP和ALPP分别从21.4±2.0和39.2±3.3mmHg降至13.1±1.5和21.6±1.9mmHg（P<0.01）。PNT术后，RLPP和ALPP分别从21.0±1.6和41.9±3.0mmHg降至13.1±1.5和24.7±3.3mmHg（P<0.01）。AT-1抑制剂使RLPP和ALPP分别从21.0±6.2和41.8±9.4mmHg显著降至12.0±3.8和25.6±6.6mmHg（P<0.01）。同样，AT-2治疗使RLPP和ALPP分别从21.4±6.3和40.1±1.7mmHg降至13.5±5.7和31.0±7.2mmHg（P<0.01）。手术后，给予Ang-II可使RLPP和ALPP恢复到术前基线值。
AT-1和AT-2受体抑制可显著降低尿道阻力，与神经源性或尿道松解性损伤相当。Ang-II治疗可恢复内在括约肌功能障碍大鼠的尿道张力。Ang II似乎在维持尿道张力和压力性尿失禁方面发挥功能性作用。
