Sasatomi Kurumi, Hiragata Shiro, Miyazato Minoru, Chancellor Michael B, Morris Sidney M, Yoshimura Naoki
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Urology. 2008 Sep;72(3):696-700. doi: 10.1016/j.urology.2007.12.002. Epub 2008 Mar 21.
We investigated the effects of an arginase inhibitor on bladder overactivity and measured bladder arginase I and II mRNA levels in rats with chronic spinal cord injury (SCI).
We performed awake cystometrograms 3 to 4 weeks after spinal cord transection in female rats. Cystometric parameters such as mean amplitudes and number of non-voiding contractions (NVCs), voided volume, voiding efficiency, and micturition pressure were evaluated before and after intravenous (i.v.) injection of an arginase inhibitor (nor-NOHA: N(omega)-hydroxy-nor-L-arginine) in SCI rats. We also examined the effects of an NOS inhibitor (L-NAME: N(omega)-nitro-L-arginine methyl ester hydrochloride) to determine whether suppression of bladder overactivity by arginase inhibition is mediated by increased production of NO. In addition, we measured mRNA levels of arginase I and II in SCI bladders using quantitative real-time polymerase chain reaction (qRT-PCR).
We found that nor-NOHA (10 mg/kg, i.v.) significantly decreased the amplitude and number of NVCs. There were no significant changes in other parameters before and after administration of vehicle or nor-NOHA at any dose. When we administered L-NAME (20 mg/kg, i.v.) before nor-NOHA injection (10 mg/kg, i.v.), nor-NOHA-induced inhibition of NVCs was prevented. The relative levels of both arginase I and II mRNA in the bladder were significantly higher in SCI rats compared with spinal cord-intact rats.
These results suggest that arginase inhibition can suppress SCI-induced bladder overactivity as indicated by a reduction in NVCs. Thus, arginase inhibition could be an effective treatment for neurogenic bladder overactivity in pathological conditions such as SCI.
我们研究了一种精氨酸酶抑制剂对膀胱过度活动症的影响，并测量了慢性脊髓损伤（SCI）大鼠膀胱中精氨酸酶I和II的mRNA水平。
在雌性大鼠脊髓横断后3至4周进行清醒膀胱测压。在脊髓损伤大鼠静脉注射（i.v.）精氨酸酶抑制剂（nor-NOHA：N（ω）-羟基-nor-L-精氨酸）之前和之后，评估膀胱测压参数，如平均幅度和非排尿收缩（NVCs）的数量、排尿量、排尿效率和排尿压力。我们还研究了一氧化氮合酶抑制剂（L-NAME：N（ω）-硝基-L-精氨酸甲酯盐酸盐）的作用，以确定精氨酸酶抑制对膀胱过度活动症的抑制作用是否由一氧化氮生成增加介导。此外，我们使用定量实时聚合酶链反应（qRT-PCR）测量脊髓损伤膀胱中精氨酸酶I和II的mRNA水平。
我们发现nor-NOHA（10mg/kg，i.v.）显著降低了NVCs的幅度和数量。在给予载体或任何剂量的nor-NOHA之前和之后，其他参数均无显著变化。当我们在注射nor-NOHA（10mg/kg，i.v.）之前给予L-NAME（20mg/kg，i.v.）时，nor-NOHA诱导的NVCs抑制作用被阻止。与脊髓完整的大鼠相比，脊髓损伤大鼠膀胱中精氨酸酶I和II mRNA的相对水平显著更高。
这些结果表明，精氨酸酶抑制可以抑制脊髓损伤诱导的膀胱过度活动症，表现为NVCs减少。因此，精氨酸酶抑制可能是治疗脊髓损伤等病理状态下神经源性膀胱过度活动症的有效方法。
