Effects of adrenergic alpha2-receptor agonists on urinary bladder contraction in conscious rats

We investigated the effects of the adrenergic alpha2-receptor agonists clonidine, oxymetazoline and tizanidine on bladder contractions induced by infusing fluid into the bladders of conscious male rats. I.v. clonidine and oxymetazoline (both 0.01 to 0.1 mg/kg) caused bladder hyperactivity, expressed by shortening of the intercontraction interval. Tizanidine (0.1 mg/kg, i.v.) caused slight shortening of the intercontraction interval. The rank order of potency was clonidine = oxymetazoline >> tizanidine. Intrathecal (i.t.) injection of 10 microg clonidine and oxymetazoline, and intracerebroventricular (i.c.v) injection at 15 microg, produced almost the same pattern of bladder hyperactivity as that observed after i.v. injection of these drugs (0.03 mg/kg, i.v.). For all three administration routes of clonidine and oxymetazoline, i.v. idazoxan (0.3 mg/kg) exerted an inhibitory effect on the bladder hyperactivity induced by these drugs, except i.c.v injection of oxymetazoline. I.t. phenylephrine (30 microg) did not change the intercontraction interval. Although i.c.v. phenylephrine (15 microg) shortened the intercontraction interval, the potency was weaker than those of i.c.v. clonidine and oxymetazoline (15 microg). These results suggest that clonidine and oxymetazoline cause bladder hyperactivity by acting at adrenergic alpha2 receptors in the micturition centers of the lumbosacral and supraspinal regions.