Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Department of Urology, Nara Medical University, Kashihara, Japan.
Am J Physiol Renal Physiol. 2022 Oct 1;323(4):F447-F454. doi: 10.1152/ajprenal.00105.2022. Epub 2022 Aug 11.
We aimed to evaluate the effects of a soluble guanylate cyclase (sGC) activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury (SCI). Mice were divided into the following three groups: spinal cord intact (), SCI + vehicle (), and SCI + BAY 60-2770 (). SCI mice underwent Th8-Th9 spinal cord transection and treatment with BAY 60-2770 (10 mg/kg/day) once daily for 2-4 wk after SCI. We evaluated urodynamic parameters using awake cystometry and external urethral sphincter electromyograms (EMG); mRNA levels of mechanosensory channels, nitric oxide (NO)-, ischemia-, and inflammation-related markers in L6-S1 dorsal root ganglia, the urethra, and bladder tissues; and protein levels of cGMP in the urethra at 4 wk after SCI. With awake cystometry, nonvoiding contractions, postvoid residual, and bladder capacity were significantly larger in than in . Voiding efficiency (VE) was significantly higher in than in . In external urethral sphincter EMGs, the duration of notch-like reductions in intravesical pressure and reduced EMG activity time were significantly longer in than in . mRNA expression levels of transient receptor potential ankyrin 1, transient receptor potential vanilloid 1, acid-sensing ion channel (ASIC)1, ASIC2, ASIC3, and Piezo2 in the dorsal root ganglia, and hypoxia-inducible factor-1α, VEGF, and transforming growth factor-β1 in the bladder were significantly higher in than in and . mRNA levels of neuronal NO synthase, endothelial NO synthase, and sGCα1 and protein levels of cGMP in the urethra were significantly lower in than in and . sGC modulation might be useful for the treatment of SCI-related neurogenic lower urinary tract dysfunction. This is the first report to evaluate the effects of a soluble guanylate cyclase activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury.
我们旨在评估可溶性鸟苷酸环化酶（sGC）激活剂 BAY 60-2770 对脊髓损伤（SCI）小鼠神经原性下尿路功能障碍的影响。将小鼠分为以下三组：脊髓完整组（）、SCI+ vehicle 组（）和 SCI+BAY 60-2770 组（）。SCI 小鼠接受 Th8-Th9 脊髓横断，并在 SCI 后每天用 BAY 60-2770（10mg/kg/天）治疗 2-4 周。我们使用清醒膀胱测压法和尿道外括约肌肌电图（EMG）评估尿动力学参数；L6-S1 背根神经节、尿道和膀胱组织中机械感觉通道、一氧化氮（NO）-、缺血-和炎症相关标志物的 mRNA 水平；以及 SCI 后 4 周尿道中环鸟苷酸（cGMP）的蛋白水平。通过清醒膀胱测压法，非排尿收缩、排尿后残余尿量和膀胱容量在 组中明显大于 组。在尿道外括约肌 EMG 中，膀胱内压力 Notch 样减少和 EMG 活动时间减少的持续时间在 组中明显长于 组。背根神经节中瞬时受体电位锚蛋白 1、瞬时受体电位香草素 1、酸感应离子通道（ASIC）1、ASIC2、ASIC3 和 Piezo2 的 mRNA 表达水平，以及膀胱中的缺氧诱导因子-1α、VEGF 和转化生长因子-β1 在 组中明显高于 组和 组。尿道中神经元型一氧化氮合酶、内皮型一氧化氮合酶和 sGCα1 的 mRNA 水平以及 cGMP 的蛋白水平在 组中明显低于 组和 组。sGC 调节可能对治疗 SCI 相关的神经原性下尿路功能障碍有用。这是首次评估可溶性鸟苷酸环化酶激活剂 BAY 60-2770 对脊髓损伤小鼠神经原性下尿路功能障碍的影响。
