EFFECTS OF PARTIAL OUTLET OBSTRUCTION OF THE RAT URINARY-BLADDER ON MICTURITION CHARACTERISTICS, DNA-SYNTHESIS AND THE CONTRACTILE RESPONSE TO FIELD STIMULATION AND PHARMACOLOGICAL AGENTS

Partial outlet obstruction is one of the major urological complications induced by benign prostatic hypertrophy (BPH). The current study describes the time course of the effect of mild partial outlet obstruction (in rats) on in vivo micturition parameters, DNA synthesis, and on the in vitro response of the bladder to field stimulation, bethanechol, methoxamine, ATP, and KCl. Mild partial outflow obstruction was created by placing a catheter (outside diameter: 1.70 mm.) transabdominally in front of the urethra, tying a ligature (2-zero silk) around both the urethra and catheter, and then removing the catheter. The micturition pattern was monitored for 2 days prior to surgery, and then continuously for 14 days following the surgery. The changes in bladder weight and the in vitro detrusor function of control (sham operated) and obstructed bladders (1, 3, 5, 7, 14 and 28 days after surgery) were examined. Micturition frequency in the dark cycle decreased immediately after the operation, and then increased linearly reaching a maximum at the 5th day, and stabilized at this increased level for the duration of the micturition study. The frequency of the dark cycle was also decreased immediately after the sham surgery and then gradually increased over the period of observation. Bladder weight increased by day 1 following surgery, and remained high throughout the 28 day study. The contractile response of the obstructed bladder base to field stimulation was reduced at days 1 and 3. The response then increased above control for day 5, reached a maximum response at day 7 and remained at this level for days 14 and 28. A similar pattern was observed for the contractile response of the bladder body to bethanechol and KCl, and for the bladder base to methoxamine and KCl. Both obstructed and sham surgeries increased bladder DNA content and H-3-thymidine incorporation, which reached maximal values on days 5 and 3, respectively. DNA content and H-3-thymidine incorporation of obstructed bladders were greater than those of sham operated bladders. In conclusion, partial outlet obstruction in the rat resulted in a progressive increase in bladder mass, an increase in micturition frequency, increases in the in vitro contractile response to field stimulation, bethanechol, methoxamine, and KCl, and increases in bladder DNA content and H-3-thymidine incorporation.