Christ George J, Day Nancy S, Day Michele, Zhao Weixin, Persson Katarina, Pandita Raj K, Andersson Karl-Erik
Departments of Urology and Physiology and Biophysics, Institute for Smooth Muscle Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Am J Physiol Regul Integr Comp Physiol. 2003 May;284(5):R1241-8. doi: 10.1152/ajpregu.00030.2002.
Bladder overactivity associated with outflow obstruction is a common human condition recapitulated in the female rat by narrowing the diameter of the urethra. The goal of these studies was to evaluate the role of intercellular communication through connexin43 (Cx43)-derived gap junction channels to bladder overactivity following partial urethral outflow obstruction of 3-day to 6-wk duration. Cx43 mRNA and protein expression were barely detectable by Northern or Western blots, respectively, in the detrusor layer of normal bladders, but bands were found with both techniques after 6 wk of obstruction. Linear regression analysis of the RT-PCR data revealed a statistically significant positive correlation between the duration of obstruction (again, ranging from 3-day to 6-wk duration) and Cx43 mRNA transcript levels, such that after 6 wk of obstruction, Cx43 transcript levels were approximately 15-fold greater than initial control values. When taking into account the approximately fivefold increase in bladder weight over this same time frame, the absolute amount of Cx43 mRNA in the bladder apparently increased by approximately 75-fold. In that regard, as anticipated, and consistent with previous observations, 6 wk of obstruction was also associated with a significant increase in spontaneous bladder contractions between micturitions. The amplitude of these contractions was significantly reduced by heptanol given intravesically. Furthermore, carbachol-precontracted bladder strips from obstructed animals were more sensitive to heptanol-induced relaxation (100 microM) than their unobstructed counterparts (n = 6; P < 0.01). When bladder strips were equivalently precontracted via electrical field stimulation (EFS; 20 Hz), similar heptanol-induced relaxation responses were observed. However, the tetrodotoxin-resistant portion of the EFS-induced contraction was greater in the obstructed than in the unobstructed animals, and this portion of the contractile response was more sensitive to heptanol-induced relaxation in obstructed than unobstructed bladders (n = 7; P < 0.01). Taken together, these observations indicate that partial outlet obstruction produces an overactive bladder that may be more dependent on intercellular communication through gap junctions for modulation of contractile responses than its normal counterpart.
与流出道梗阻相关的膀胱过度活动是一种常见的人类病症，在雌性大鼠中可通过缩小尿道直径来模拟。这些研究的目的是评估通过连接蛋白43（Cx43）衍生的缝隙连接通道进行细胞间通讯在3天至6周时长的部分尿道流出道梗阻后对膀胱过度活动的作用。在正常膀胱的逼尿肌层中，分别通过Northern印迹或Western印迹几乎检测不到Cx43 mRNA和蛋白表达，但在梗阻6周后两种技术均发现有条带。对RT-PCR数据的线性回归分析显示，梗阻持续时间（同样为3天至6周时长）与Cx43 mRNA转录水平之间存在统计学上显著的正相关，因此在梗阻6周后，Cx43转录水平比初始对照值大约高15倍。考虑到在同一时间范围内膀胱重量大约增加了五倍，膀胱中Cx43 mRNA的绝对量显然增加了大约75倍。在这方面，正如预期的那样，并且与先前的观察结果一致，梗阻6周还与排尿间期自发膀胱收缩的显著增加有关。膀胱内给予庚醇可显著降低这些收缩的幅度。此外，来自梗阻动物的卡巴胆碱预收缩膀胱条对庚醇诱导的舒张（100 microM）比未梗阻的对应物更敏感（n = 6；P < 0.01）。当通过电场刺激（EFS；20 Hz）使膀胱条等效预收缩时，观察到类似的庚醇诱导的舒张反应。然而，EFS诱导的收缩中对河豚毒素不敏感的部分在梗阻动物中比未梗阻动物更大，并且这部分收缩反应在梗阻膀胱中比未梗阻膀胱对庚醇诱导的舒张更敏感（n = 7；P < 0.01）。综上所述，这些观察结果表明，部分出口梗阻会产生膀胱过度活动，与正常膀胱相比，其可能更依赖通过缝隙连接的细胞间通讯来调节收缩反应。
