Effects of α1-adrenergic receptor subtype selective antagonists on lower urinary tract function in rats with bladder outlet obstruction

Purpose: Antagonists of α₁-adrenergic receptors (α₁ARs) relieve obstructive and irritative symptoms in patients with bladder outlet obstruction. However, to our knowledge mechanisms underlying the relief of irritative symptoms remain unknown. Because bladder α_1dARs are up-regulated in some rats with bladder outlet obstruction, we investigated the effect of the α_1aAR antagonist 5-methyl urapidil (5MU) vs the α_1a/α_1dAR antagonist tamsulosin on urinary frequency in obstructed rats. Materials and Methods: Baseline frequency was measured using a chronic micturition recording system and then obstruction (40 rats) or sham obstruction surgery (11 rats) was performed. After 6 weeks frequency was reassessed, followed by subcutaneous implantation of osmotic pumps to deliver 5MU, tamsulosin or vehicle for 1 week. Upon the completion of drug treatment urinary frequency was again measured and the pressor response to the α₁AR agonist phenylephrine was documented. Results: Obstructed bladder mass was an average of 4.9 times greater than bladder mass in sham operated rats (p <0.001). Urinary frequency was elevated in obstructed rats with a bladder mass of greater than 500 mg vs all rats with a bladder mass of under 255 mg (p = 0.01). Of rats with a bladder mass of greater than 500 mg frequency was decreased in those treated with tamsulosin (p = 0.03) but not in those treated with 5MU. Tamsulosin and 5MU inhibited the pressor response to phenylephrine. Conclusions: Urinary frequency is increased in rats with a bladder mass of greater than 500 mg. The combined α_1a/α_1dAR antagonist tamsulosin decreases urinary frequency more than the α_1aAR selective antagonist 5MU. This finding supports the hypothesis that the α_1dAR is important for mediating irritative symptoms.