Effects of vasopressin receptor agonists on detrusor smooth muscle tone in young and aged bladders: Implications for nocturia treatment

作者：Youko Ikeda, Irina V. Zabbarova, Mathijs M. de Rijk, Anthony Kanai, Amanda Wolf‐Johnston, Jeffrey P. Weiss, Edwin Kerry Jackson, Lori Ann Birder · 发表于：Continence · 年份：2022 · DOI：10.1016/j.cont.2022.100032 · 被引用次数：12 · 研究领域：Urinary Bladder and Prostate Research、Neuroendocrine regulation and behavior、Pelvic floor disorders treatments

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 (V1Rs) and vasopressin-2 receptor (V2Rs), 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 (V2R 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 V1Rs causing contraction and V2Rs relaxation. In aged bladders, the contractile response to V1R activation is attenuated due to release of a mucosal factor that attenuates V1R-induced contractions. Also in aged bla...