Role of the beta(3)-adrenoceptor in urine storage in the rat: Comparison between the selective beta(3)-adrenoceptor agonist, CL316,243, and various smooth muscle relaxants

The objective of this study was to compare the effects of a beta(3)-adrenoc eptor (beta(3)-AR) agonist on bladder function and cardiovascular parameter s in rats with those of several drugs that act on smooth muscle. CL316,243 (beta(3)-AR agonist), isoproterenol (nonselective beta-AR agonist), procate rol (beta(2)-AR agonist), verapamil (Ca2+ antagonist), and papaverine (anti spastic drug) each evoked a concentration-dependent relaxation of the detru sor in vitro. They also reduced bladder pressure in anesthetized rats, the beta-AR agonists apparently being more potent than the other drugs. Atropin e (muscarinic antagonist) neither relaxed detrusor strips nor reduced bladd er pressure. In anesthetized rats, CL316,243 and atropine each had only a s light influence on blood pressure and heart rate, but isoproterenol, procat erol, verapamil, and papaverine significantly affected cardiovascular funct ion at the same dose range as that required to reduce bladder pressure. In cystometry experiments, CL316,243 (10 mu g/kg i.v.), verapamil (1 mg/kg i.v .), and papaverine(1 mg/kg i.v.) all significantly prolonged micturition in terval and increased bladder capacity, but did not change the residual urin e volume after a micturition contraction. Procaterol (100 mu g/kg i.v.) pro longed the micturition interval and increased both bladder capacity and res idual urine volume (all significantly). Atropine (100 mu g/kg i.v.) reduced micturition pressure and increased residual urine volume (both significant ly). Because the human detrusor, like the rat detrusor, relaxes on beta(3)- AR stimulation, we conclude that this beta(3)-AR agonist may have potential in pollakiuria (frequent urination) as a therapeutic agent without cardiov ascular side effects.