Effects of β3-adrenoceptor stimulation on prostaglandin E2–induced bladder hyperactivity and on the cardiovascular system in conscious rats


  • Part of this investigation was presented at the International Continence Society 30th Annual Meeting [Takeda H. et al., 2000b].



To investigate the effects of selective β2- and selective β3-adrenoceptor (AR) agonists on prostaglandin (PG) E2-induced bladder hyperactivity in conscious free-moving rats.


Female Sprague-Dawley rats were anesthetized for implantation of bladder, intravenous, and intra-arterial catheters. The effects of a β3-AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats. Intravesical instillation of PGE2 (20–60 μM, 6 mL/hr) in conscious rats produced a concentration-dependent increase in voiding frequency.


In this model i.v. CL316,243 (β3-AR agonist) reduced basal bladder pressure, increased micturition volume, and prolonged micturition interval in a dose-dependent manner, without affecting threshold pressure or micturition pressure. On the other hand, i.v. procaterol (β2-AR agonist) did not counteract the bladder hyperactivity. Atropine (muscarinic antagonist) reduced micturition pressure and micturition volume, and shortened micturition interval. CL316,243 slightly decreased mean blood pressure and increased heart rate only when given at high doses (10 and 100 μg/kg, i.v.). In contrast, procaterol caused a significant decrease in mean blood pressure and a significant increase in heart rate. Atropine significantly increased heart rate.


The present results clearly demonstrated that the β3-AR agonist prolonged the micturition interval without producing significant cardiovascular side effects. The human detrusor, like the rat detrusor, relaxes on β3-AR stimulation. Provided that these results are valid in humans, selective β3-AR agonists might be clinically useful for controlling a certain type of bladder overactivity. Neurourol. Urodynam. 21:558–565, 2002. © 2002 Wiley-Liss, Inc.