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

Abstract

The present results clearly demonstrated that the beta(3)-AR agonist prolonged the micturition interval without producing significant cardiovascular side effects. The human detrusor, like the rat detrusor, relaxes on beta(3)-AR stimulation. Provided that these results are valid in humans, selective beta(3)-AR agonists might be clinically useful for controlling a certain type of bladder overactivity.

Enhanced Sensitivity to Afferent Stimulation and Impact of Overactive Bladder Therapies in the Conscious, Spontaneously Hypertensive Rat

“…The ability of muscarinic antagonism to reduce MP in multiple species, including rats, is well documented (Angelico et al, 2005;Ney et al, 2008;McCafferty et al, 2009). Likewise, MI shortening and VV reduction in the SHR in response to muscarinic antagonism is consistent with previous rat studies (Igawa et al, 1993;Takeda et al, 2000Takeda et al, , 2002Ney et al, 2008). Overall, our urodynamic observations in response to muscarinic antagonism in the SHR are consistent with previous findings in cystometric studies of normal rats.…”

Effects of Ritobegron (KUC-7483), a Novel Selective β3-Adrenoceptor Agonist, on Bladder Function in Cynomolgus Monkey

“…These results are consistent with previous reports that selective ␤ 3 -AR agonists improve bladder functions in rats with minimal effects on the cardiovascular system (Takeda et al, 2000b(Takeda et al, , 2002bKaidoh et al, 2002). Moreover, when we measured the plasma concentration of ritobegron in cynomolgus monkeys that had received on intraduodenal administration of 1, 3, or 10 mg/kg the maximum plasma values we obtained were 3.7 ϫ 10 Ϫ7 , 1.3 ϫ 10…”

GW427353 (Solabegron), a Novel, Selective β3-Adrenergic Receptor Agonist, Evokes Bladder Relaxation and Increases Micturition Reflex Threshold in the Dog

“…D. Westfall, unpublished observations). In rat models, ␤ 3 -AR agonists have been shown to increase micturition interval in bladder instability evoked by cerebral infarction (Kaidoh et al, 2002), intravesical acetic acid or prostaglandin E 2 (Woods et al, 2001;Takeda et al, 2002b); inhibit sponta- jpet.aspetjournals.org neous intermicturition contractions in obstruction-induced bladder hyperplasia (Woods et al, 2001); and decrease the frequency of rhythmic bladder contractions (Takasu et al, 2007). ␤ 3 -AR-mediated bladder relaxation is also observed in the anesthetized ferret (Takeda et al, 2000).…”