TY - JOUR T1 - Effects of the β3-Adrenergic Receptor Agonist Disodium 5-[(2<em>R</em>)-2-[[(2<em>R</em>)-2-(3-Chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316243) on Bladder Micturition Reflex in Spontaneously Hypertensive Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 178 LP - 185 DO - 10.1124/jpet.108.138651 VL - 326 IS - 1 AU - Lisa A. Leon AU - Bryan E. Hoffman AU - Scott D. Gardner AU - Nicholas J. Laping AU - Christopher Evans AU - Erin S. R. Lashinger AU - Xin Su Y1 - 2008/07/01 UR - http://jpet.aspetjournals.org/content/326/1/178.abstract N2 - The present study investigated whether β3-adrenoceptor activation acts on the bladder afferent pathway by examination of the visceromotor reflex (VMR) and pressor responses to urinary bladder distension (UBD) and whether β3-adrenoceptor activation produces urinary bladder relaxation in hyperactive spontaneously hypertensive rats (SHRs) in comparison with their normotensive control rats [Wistar-Kyoto (WKY)]. Using the VMR responses to noxious UBD as a measure of bladder afferent signal transmission, SHRs did not present a sensitized bladder phenotype. However, reduced bladder compliance accompanied by a reduced void threshold was detected in the SHR detrusor. Furthermore, the selective β3-adrenoceptor agonist disodium 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316243) (i.v.) failed to attenuate VMR or pressor responses to UBD in either SHRs or WKY rats, but it dose-dependently inhibited rhythmic contraction (RC) in SHRs. The minimal effective dose was 0.001 mg/kg. Using the same model in WKY rats, CL-316243 did not elicit significant inhibition of contractions in the bladder RC assay. These results suggest that SHRs represent abnormal efferent/detrusor function (detrusor overactivity) without mechanosensory afferent hypersensitivity. The β3-adrenoceptor agonist CL-316243 acts on the detrusor muscle to increase urine storage in SHRs. The American Society for Pharmacology and Experimental Therapeutics ER -