Effect of botulinum toxin A on the autonomic nervous system of the rat lower urinary tract

Purpose: The magnitude and duration of the effects of botulinum toxin A on acetylcholine (ACh) and norepinephrine release from the bladder and urethra of rats were measured using a radiochemical method. Materials and Methods: Saline (sham treatment) or botulinum toxin A was injected into the bladder (50 mul.) or urethra (30 mul.) in separate groups of animals. The release of H-3-norepinephrine or C-14-choline was measured at 2 time points after injection (5 or 30 days). Results: The fractional release of ACh in botulinum. toxin A treated animals was significantly inhibited at higher frequencies of electrical field stimulation (20 Hz.) but not at lower frequencies (2 Hz.) 5 days after injection. However, ACh release recovered to sham injected values 30 days after toxin injection. No significant differences in the fractional release of norepinephrine from sham injected or botulinum toxin A bladders were observed. In contrast, norepinephrine release from the urethra was inhibited by botulinum. toxin A for at least 30 days after injection. Similar to its effect on transmitter release in the bladder, botulinum toxin A inhibited norepinephrine release in the urethra at high (20 Hz.) but not at low (4 Hz.) electrical stimulation frequencies. Conclusions: These data indicate that the clinical effects of botulinum. toxin A on the lower urinary tract may vary depending on the site of injection and level of nerve activity.