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

PURPOSE: 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. RESULTS: In young rat bladders, AVP, an agonist at both vasopressin-1 receptors (V(1)Rs) and vasopressin-2 receptor (V(2)Rs), 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 (V(2)R selective agonist) relaxed bladder strips. This response was reduced by removal of the mucosa in young, but not aged, bladder strips. CONCLUSION: These findings support a direct role for VRs in regulating detrusor tone with V(1)Rs causing contraction and V(2)Rs relaxation. In aged bladders, the contractile response to V(1)R activation is attenuated due to release of a mucosal factor that attenuates V(1)R-induced contractions. Also in aged bladders, the relaxation response to V(2)R activation is attenuated by lack of release of a mucosal factor that contributes to V(2)R-induced relaxation. Thus age-associated changes in the bladder mucosa impair the effects of VRs on bladder tone. Because the V(2)R signaling system is impaired in the older bladder, administering an exogenous V(2)R 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.