Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
Department of Urology, Ludwig-Maximilians-University of Munich, Munich, Germany.
World J Urol. 2023 Sep;41(9):2541-2547. doi: 10.1007/s00345-023-04528-3. Epub 2023 Aug 1.
Aim of this study was to evaluate the effect of intravenous Y27632 (a ROK inhibitor) on intra-ureteral pressures and on blood pressure in an in vivo rat model for unilateral partial ureteral obstruction (PUO).
15 Male Sprague Dawley rats were used. Under isofluran anesthesia, saline was continuously infused via polyethylene (PE)-10 catheters inserted in the ureters beneath the kidney pelvis. Left psoas muscle was sutured around the distal left ureter to create a partial obstruction. Carotid artery and femoral vein were cannulated with PE catheters for registration of mean arterial blood pressure (MAP) and for administration of drugs. Left and right ureter pressures and MAP were simultaneously recorded. Y27632 (0.03 and 0.1 mg/kg each n = 6-7) was given intravenously. T-test was used for comparisons.
Spontaneous peristaltic pressure waves were recorded at baseline for both ureters. After the obstruction, Y27632 reduced maximum pressure (MaxP) by 10.5 ± 1.9% (0.03 mg/kg; p = 0.004) and 29.1 ± 4.8% (0.1 mg/kg; p < 0.001), minimum pressure (MinP) by 5.2 ± 2.3% (0.03 mg/kg; p = 0.02) and 12.2 ± 3.4% (0.1 mg/kg; p = 0.009), the area under the curve (AUC) by 7.8 ± 2.4% (0.03 mg/kg; p = 0.008) and 16.5 ± 3.7% (0.1 mg/kg;p = 0.007), the waves amplitude by 23.4 ± 11.3% (0.03 mg/kg; p = 0.098) and 38.7 ± 7.5% (0.1 mg/kg; p < 0.001), with no effect on contraction frequency. During simultaneous recordings from the normal ureter at the investigated doses, Y27632 reduced MaxP, MinP, AUC and waves amplitude by 1-7%. The MAP was reduced by 12.5 ± 5.3% (0.03 mg/kg; p = 0.07) and 15.8 ± 1.8% (0.1 mg/kg; p < 0.001).
Y27632 decreased intra-ureteral pressures of a partially obstructed ureter with limited effect on blood pressure in an animal model of unilateral PUO.
本研究旨在评估静脉注射 Y27632（ROK 抑制剂）对单侧部分输尿管梗阻（PUO）动物模型中输尿管内压和血压的影响。
使用 15 只雄性 Sprague Dawley 大鼠。在异氟烷麻醉下，通过聚乙烯（PE）-10 导管持续向肾盂下方的输尿管内输注盐水。左腰大肌缝合在左输尿管远端周围，造成部分梗阻。通过 PE 导管将颈总动脉和股静脉插管，用于记录平均动脉血压（MAP）和药物给药。同时记录左、右输尿管压力和 MAP。静脉给予 Y27632（0.03 和 0.1mg/kg 各 n=6-7）。采用 t 检验进行比较。
在基线时，两条输尿管均记录到自发蠕动压力波。梗阻后，Y27632 使最大压力（MaxP）降低 10.5±1.9%（0.03mg/kg；p=0.004）和 29.1±4.8%（0.1mg/kg；p<0.001），最小压力（MinP）降低 5.2±2.3%（0.03mg/kg；p=0.02）和 12.2±3.4%（0.1mg/kg；p=0.009），曲线下面积（AUC）降低 7.8±2.4%（0.03mg/kg；p=0.008）和 16.5±3.7%（0.1mg/kg；p=0.007），波幅降低 23.4±11.3%（0.03mg/kg；p=0.098）和 38.7±7.5%（0.1mg/kg；p<0.001），但对收缩频率无影响。在研究剂量下同时记录正常输尿管时，Y27632 使 MaxP、MinP、AUC 和波幅降低 1-7%。MAP 降低 12.5±5.3%（0.03mg/kg；p=0.07）和 15.8±1.8%（0.1mg/kg；p<0.001）。
Y27632 降低单侧 PUO 动物模型部分梗阻输尿管内压，对血压影响有限。
