Comparison of the effects of β3 -adrenoceptor agonism on urinary bladder function in conscious, anesthetized, and spinal cord injured rats.

AimsTo compare the dose effect relationship of a selective (3)-adrenoceptor agonist (CL-316,243) on cystometric parameters in anesthetized and conscious rats and to evaluate its effect in a model of neurogenic bladder overactivity induced by spinal cord injury (SCI). MethodsExperiments were performed in anesthetized and conscious normal rats and in conscious rats after complete transection at the T8 level of the spinal cord. The jugular vein and urinary bladder were catheterized and the bladder infused with saline. CL-316,243 was tested intravenously at 0.01, 0.03, and 0.1mg/kg in anesthetized and conscious rats and at 0.01mg/kg in sham and SCI rats. Intravesical pressure was recorded for 1hr following drug administration. Intercontraction interval (ICI), amplitude of micturition (AM), micturition frequency (MF) and non-voiding contractions (NVC) were analyzed. ResultsIn anesthetized and conscious normal rats, CL-316,243 significantly increased ICI in a dose-dependent manner. In anesthetized rats, AM was significantly decreased at all doses tested whereas in conscious rats, a significant decrease (-196%) in AM was only observed at the highest dose (0.1mg/kg). In conscious sham and SCI rats, CL-316,243 significantly increased ICI (42 +/- 17% and 49 +/- 17%, respectively) and decreased MF without affecting AM. In SCI rats, CL-316,243 reduced the frequency of NVC (-53 +/- 14%) without significant effects on amplitude. ConclusionsThe current results suggest that anesthesia can alter the effects of (3)-adrenoceptor agonists in experimental models. In addition, this is the first demonstration that stimulation of (3)-adrenoceptors can produce decreases in micturition frequency and NVC in SCI rats without affecting AM. Neurourol. Urodynam. 34:578-585, 2015. (c) 2014 Wiley Periodicals, Inc.