β-adrenoceptor agonist effects in experimental models of bladder dysfunction.

β-adrenoceptor stimulation can enhance the storage function of the urinary bladder by acting on detrusor smooth muscle tone, mediator release from the urothelium and/or afferent nerve activity. In humans this may occur predominantly if not exclusively via the β₃-subtype. The effects of β-adrenoceptor agonists including several β₃-selective agonists have been studied in vitro and in vivo, in healthy animals of both genders and various age groups and in a wide range of animal (mostly rat) models of genetic or acquired bladder dysfunction. Such models included bladder irritation by intravesical instillation of acetic acid or prostaglandin E₂, bladder outlet obstruction, stroke, diabetes, spontaneously hypertensive rats, and NO synthase inhibition. Across all of these models β-adrenoceptor agonists had effects consistent with improved bladder storage function. β₃-adrenoceptor effects are resistant to agonist-induced desensitization in many cell types, but whether this also applies to the human bladder is unknown. The efficacy of β-adrenoceptor agonists appears to be largely unaffected by common polymorphisms of the β₃-adrenoceptor gene. Taken together these findings suggest that β₃-adrenoceptor agonists may become useful drugs for the treatment of bladder storage dysfunction, a view supported by recent phase III clinical studies for one such agent, mirabegron.