Relationship of mass of obstructed rat bladders and responsiveness to adrenergic stimulation

Purpose: The effects of experimental partial bladder outlet obstruction on the bladder response to nerve stimulation and contractile agonists have been well characterized. Mildly obstructed bladders have small increases in mass and increased contractile responses to electrical field stimulation. More severely obstructed bladders become decompensated with large increases in mass and decreased functional responses. Little is known about relaxant mechanisms after obstruction. We investigated the relationship of the increase in rat bladder mass induced by outlet obstruction and responses to alpha and beta-adrenergic stimulation. Materials and Methods: Male Sprague-Dawley rats were divided into 3 groups, namely control, sham operated and obstructed. Surgical obstruction was done by tying a 2-zero silk ligature around the urethra. The ligature was placed around the urethra and removed in sham operated rats. At 2 and 6 weeks bladders from all groups were harvested, weighed and cut into strips. Contractile responses to electrical field stimulation and norepinephrine in the presence of propranolol were measured. Relaxant responses to norepinephrine and isoproterenol were measured after pre-contraction with KCl. Results: All strips from control and sham operated rats relaxed completely in response to norepinephrine. Obstructed bladders that weighed 2 to 3-fold more than control or sham operated bladders also relaxed. In contrast, bladders that were 5 to 10-fold heavier failed to relax by at least 50% in response to norepinephrine, independent of duration of bladder outlet obstruction. These were called nonresponders. Two week nonresponders relaxed completely in response to isoproterenol, but 6-week nonresponders did not, suggesting that the duration of decompensation is important. All nonresponders relaxed in response to pinacidil (Sigma-Aldrich Corp., St. Louis, Missouri). Nonresponders tended to contract in response to norepinephrine in the presence of propranolol. Strips from the other rats were less responsive, suggesting an increase in alpha1-receptors with decompensation. Contractile responses to field stimulation were increased in obstructed strips that relaxed to norepinephrine, while responses of nonresponders were decreased compared with controls and sham operated rats. Conclusions: Severely obstructed bladders had an increase in mass and a decreased response to field stimulation, indicative of decompensation. This response was accompanied by decreased ability to relax to beta-agonists and an increased response to alpha-agonists. These changes were not seen in smaller, compensated bladders. Our findings suggest a change in detrusor alpha1 and beta-adrenergic receptor density. An increase in detrusor alpha-receptors may explain the clinical efficacy of alpha-blockers in alleviating irritative voiding symptoms in men with benign prostatic hyperplasia.