Rajasekaran Mahadevan, Mehta Neal, Baquir Angelo, Kuntz Steven
Division of Urology, University of California, San Diego, Medical Center, San Diego, California 92103-8897, USA.
Urology. 2007 Apr;69(4):791-4. doi: 10.1016/j.urology.2007.01.071.
The molecular mechanisms by which potassium induces urinary bladder hyperactivity are not clear. In the present study, we tested our hypothesis that potassium chloride (KCl)-induced bladder hyperactivity might be mediated through a calcium-sensitizing RhoA-Rho-kinase pathway in an in vivo animal model using urodynamic parameters.
Two groups of adult male rats (n = 8) were anesthetized, their bladder exteriorized, and a saline-filled Intracath fixed into the bladder dome. This Intracath was connected to a pressure transducer and an infusion pump. Continuous filling cystometrograms were performed by infusing warm saline (0.04 mL/min) to obtain baseline data on each rat. The number of contractions per unit time (intercontractile intervals in seconds), pressure threshold, and peak pressure during micturition were recorded. To create bladder hyperactivity, protamine sulfate (30 mg/mL) followed by KCl (500 mM) was infused intravesically, and a continuous filling cystometrogram was again recorded. Y-27632, a specific RhoA-Rho-kinase inhibitor, was administered either intra-arterially (group 1) or intravesically (group 2) to each rat, and an additional continuous filling cystometrogram was recorded with KCl (500 mM) to observe the effects of Rho-kinase inhibition on bladder contractility.
Intravesical KCl infusion after protamine exposure resulted in significantly greater contractions and decreased the intercontractile interval (P <0.05). Y-27632 administration attenuated the effect of KCl on the contractions and intercontractile interval and decreased the mean pressure threshold.
Suppression of KCl-induced bladder contractility by the Rho-kinase inhibitor Y-27632 confirmed the involvement of this novel calcium-sensitizing RhoA-Rho-kinase pathway in mediating these smooth muscle contractions.
钾诱导膀胱活动亢进的分子机制尚不清楚。在本研究中，我们在体内动物模型中使用尿动力学参数来检验我们的假设，即氯化钾（KCl）诱导的膀胱活动亢进可能通过钙敏化的RhoA- Rho激酶途径介导。
两组成年雄性大鼠（n = 8）麻醉后，将膀胱外置，将充满生理盐水的留置导管固定于膀胱顶部。该留置导管连接到压力传感器和输液泵。通过输注温生理盐水（0.04 mL/分钟）进行连续充盈膀胱测压，以获取每只大鼠的基线数据。记录单位时间内的收缩次数（收缩间隔时间，以秒为单位）、排尿压力阈值和峰值压力。为了诱导膀胱活动亢进，膀胱内注入硫酸鱼精蛋白（30 mg/mL），随后注入KCl（500 mM），并再次记录连续充盈膀胱测压。向每只大鼠动脉内（第1组）或膀胱内（第2组）给予特异性RhoA- Rho激酶抑制剂Y-27632，并在注入KCl（500 mM）的情况下再次记录连续充盈膀胱测压，以观察Rho激酶抑制对膀胱收缩力的影响。
鱼精蛋白暴露后膀胱内注入KCl导致收缩明显增强，收缩间隔时间缩短（P <0.05）。给予Y-27632可减弱KCl对收缩和收缩间隔时间的影响，并降低平均压力阈值。
Rho激酶抑制剂Y-27632对KCl诱导的膀胱收缩力的抑制作用证实了这种新型钙敏化RhoA- Rho激酶途径参与介导这些平滑肌收缩。
