In Vitro Responses of Alpha-adrenergic Antagonist of Rat Detrusor Muscle after Partial Bladder Outlet Obstruction

Kim, Young Don; Lee, Jeong Gu

Abstract

PURPOSE: Our experiments were done to determine the effects of alpha-1-adrenergic antagonists which have been commonly used in the treatment of BPH against the partially obstructed detrusor smooth muscle using in-vitro muscle strip study of female rat bladder.
MATERIALS AND METHODS
Partial obstruction was created by means of partial ligation of the proximal urethra in 15 female Sprague-Dawley rats. After 6 weeks of obstruction, 1x0.5cm sized each bladder smooth muscle strip was stimulated by field stimulation(FS),(1-32Hz) and bethanechol administration(10(-7)-10(-4)M). After the control stimulations, each strip was pre-treated with doxazosin, tamsulosin, prazosin and atropine for 30 minutes, and then same stimulations were repeated. Seperate strip was pre-treated by propranolol for 30 minutes, and then was stimulated by norepinephrine(10(-4)M) or phenylephrine(10(-4)M).
RESULTS
After the administration of doxazosin, percent decreases of maximal tension developed by FS was significantly greater in obstructed(26-50% of the control) than in normal rats(0-12% of the control)(p<0.05). Field stimulated tension were inhibited more in normal(32-40%) than in obstructed rats(p<0.05, 1-32Hz) after the administration of prazosin. Atropine inhibited field stimulated tension to a greater degree in normal(73-63%) than in obstructed(27-43%) rats(p<0.01, 1-32Hz). Complete inhibitory effects of atropine against bethanechol stimulation(10(-7)-10(-4)M) was achieved at 10(-5)M in normal rats. In obstructed rats, complete blockage was achieved at 10-4M of bethanechol. Norepinephrine decreased basal tension both in normal and obstructed rats. After pre-treatment of propranolol, phenylephrine and norepinephrine did not show any increase of basal tension.
CONCLUSIONS
Our results suggest that changes of adrenoceptors may be the underlying cause of bladder instability secondary to outflow obstruction as evidenced by significant inhibition of the tension of the detrusor muscle by alpha-1-adrenoceptor blocker(doxazosin but not by tamsulosin) only in obstructed rat bladder. These results also suggest that non-cholinergic components of bladder contraction are much more in obstructed than in normal bladder. It also can be said that doxazosin may have additional effects against bladder instability caused by BPH.