Zou Suo, Shimizu Takahiro, Yamamoto Masaki, Shimizu Shogo, Higashi Youichirou, Karashima Takashi, Saito Motoaki
Departments of, Department of, Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
Department of, Urology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan.
Int J Urol. 2021 Apr;28(4):459-465. doi: 10.1111/iju.14478. Epub 2021 Jan 5.
To investigate whether a response to hydrogen sulfide donors (GYY4137 and sodium hydrosulfide) and the endogenous hydrogen sulfide system (hydrogen sulfide level and expression of cysteine aminotransferase, cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase) in the spontaneously hypertensive rat bladder differ with age, we compared the responses of hydrogen sulfide donors to micturition and bladder relaxation, and the endogenous hydrogen sulfide system in the bladder of 18-week versus 12-week-old spontaneously hypertensive rats.
GYY4137 was intravesically administered and cystometry was performed in anesthetized rats. The responses of sodium hydrosulfide were evaluated in carbachol-mediated precontracted bladder strips. Bladder hydrogen sulfide levels and expression levels of each enzyme were investigated using the methylene blue method and Western blotting, respectively.
GYY4137 treatment significantly prolonged intercontraction intervals only in 12-week-old rats. Sodium hydrosulfide-induced bladder relaxation was significantly attenuated in the strips of 18-week-old rats compared with that in 12-week-old rats. In the bladder dome, significant increases in hydrogen sulfide levels and in the expression of cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and cysteine aminotransferase were observed in 18-week-old rats compared with 12-week-old rats. However, cystathionine γ-lyase bands were not detected in bladder tissues of either group.
Bladder relaxation induced by hydrogen sulfide may be attenuated in spontaneously hypertensive rats in an age-dependent manner.
为了研究自发性高血压大鼠膀胱对硫化氢供体(GYY4137和氢硫化钠)的反应以及内源性硫化氢系统(硫化氢水平和半胱氨酸转氨酶、胱硫醚β合酶、胱硫醚γ裂解酶和3-巯基丙酮酸硫转移酶的表达)是否随年龄而不同,我们比较了18周龄和12周龄自发性高血压大鼠膀胱中硫化氢供体对排尿和膀胱舒张的反应以及内源性硫化氢系统。
对麻醉大鼠膀胱内给予GYY4137并进行膀胱测压。在卡巴胆碱介导的预收缩膀胱条上评估氢硫化钠的反应。分别使用亚甲蓝法和蛋白质免疫印迹法研究膀胱硫化氢水平和每种酶的表达水平。
GYY4137处理仅在12周龄大鼠中显著延长了收缩间期。与12周龄大鼠相比,18周龄大鼠的膀胱条中氢硫化钠诱导的膀胱舒张明显减弱。在膀胱顶部,与12周龄大鼠相比,18周龄大鼠的硫化氢水平以及胱硫醚β合酶、3-巯基丙酮酸硫转移酶和半胱氨酸转氨酶的表达显著增加。然而,两组的膀胱组织中均未检测到胱硫醚γ裂解酶条带。
硫化氢诱导的膀胱舒张在自发性高血压大鼠中可能会以年龄依赖的方式减弱。