EFFECTS OF α 1-ADRENERGIC RECEPTOR SUBTYPE SELECTIVE ANTAGONISTS ON LOWER URINARY TRACT FUNCTION IN RATS WITH BLADDER OUTLET OBSTRUCTION

Abstract

Antagonists of alpha 1-adrenergic receptors (alpha 1ARs) 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 alpha 1dARs are up-regulated in some rats with bladder outlet obstruction, we investigated the effect of the alpha 1aAR antagonist 5-methyl urapidil (5MU) vs the alpha 1a/alpha 1dAR antagonist tamsulosin on urinary frequency in obstructed rats. 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 alpha 1AR agonist phenylephrine was documented. 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. Urinary frequency is increased in rats with a bladder mass of greater than 500 mg. The combined alpha 1a/alpha 1dAR antagonist tamsulosin decreases urinary frequency more than the alpha 1aAR selective antagonist 5MU. This finding supports the hypothesis that the alpha 1dAR is important for mediating irritative symptoms.