Ikeda Youko, Zabbarova Irina, de Rijk Mathijs, Kanai Anthony, Wolf-Johnston Amanda, Weiss Jeffrey P, Jackson Edwin, Birder Lori
University of Pittsburgh, School of Medicine, Renal-Electrolyte division, United States of America.
University of Pittsburgh, School of Medicine, Department of Pharmacology and Chemical Biology, United States of America.
Continence (Amst). 2022 Jun;2. doi: 10.1016/j.cont.2022.100032. Epub 2022 May 25.
The main goal of this study was to determine the effects of arginine vasopressin (AVP) and desmopressin on bladder contractility and to examine whether the effects of these vasopressin receptor (VR) agonists differ in young versus aged animals. These aims were addressed using urinary bladders from young (3 months) and aged (24 month) female Fischer 344 rats that were isolated and dissected into strips for isometric tension recordings. Bladder strips were exposed to AVP and desmopressin through the perfusate, and tension changes recorded.
In young rat bladders, AVP, an agonist at both vasopressin-1 receptors (VRs) and vasopressin-2 receptor (VRs), concentration-dependently caused contraction of bladder strips with a sensitivity that was greater in young versus aged bladder strips. Removal of the mucosa did not alter the sensitivity of young bladder strips to AVP yet enhanced the AVP sensitivity of aged bladder strips. The differential sensitivity to AVP between young denuded and aged denuded bladder strips was similar. In contrast to AVP, desmopressin (VR selective agonist) relaxed bladder strips. This response was reduced by removal of the mucosa in young, but not aged, bladder strips.
These findings support a direct role for VRs in regulating detrusor tone with VRs causing contraction and VRs relaxation. In aged bladders, the contractile response to VR activation is attenuated due to release of a mucosal factor that attenuates VR-induced contractions. Also in aged bladders, the relaxation response to VR activation is attenuated by lack of release of a mucosal factor that contributes to VR-induced relaxation. Thus age-associated changes in the bladder mucosa impair the effects of VRs on bladder tone. Because the VR signaling system is impaired in the older bladder, administering an exogenous VR agonist (e.g., desmopressin) could counteract this defect. Thus, desmopressin could potentially increase nighttime bladder capacity through detrusor relaxation in concert with decreased urine production, reducing nocturnal voiding frequency.
本研究的主要目的是确定精氨酸加压素（AVP）和去氨加压素对膀胱收缩力的影响，并研究这些加压素受体（VR）激动剂在年轻动物和老年动物中的作用是否存在差异。通过使用来自年轻（3个月）和老年（24个月）雌性Fischer 344大鼠的膀胱来实现这些目标，将其分离并切成条带以进行等长张力记录。膀胱条带通过灌注液暴露于AVP和去氨加压素，并记录张力变化。
在年轻大鼠膀胱中，AVP作为血管加压素1受体（VRs）和血管加压素2受体（VRs）的激动剂，浓度依赖性地引起膀胱条带收缩，年轻膀胱条带的敏感性高于老年膀胱条带。去除黏膜不会改变年轻膀胱条带对AVP的敏感性，但会增强老年膀胱条带对AVP的敏感性。年轻去黏膜和老年去黏膜膀胱条带对AVP的敏感性差异相似。与AVP相反，去氨加压素（VR选择性激动剂）使膀胱条带松弛。在年轻膀胱条带中，去除黏膜会减弱这种反应，但在老年膀胱条带中则不会。
这些发现支持VRs在调节逼尿肌张力中起直接作用，VRs引起收缩，而VRs引起松弛。在老年膀胱中，由于黏膜因子的释放减弱了VR诱导的收缩，对VR激活的收缩反应减弱。同样在老年膀胱中，由于缺乏有助于VR诱导松弛的黏膜因子的释放，对VR激活的松弛反应减弱。因此，膀胱黏膜与年龄相关的变化会损害VRs对膀胱张力的影响。由于老年膀胱中的VR信号系统受损，给予外源性VR激动剂（如去氨加压素）可以抵消这一缺陷。因此，去氨加压素可能通过与减少尿液生成协同作用使逼尿肌松弛，从而潜在地增加夜间膀胱容量，减少夜间排尿频率。
Zotero 插件
