Interaction between neurotransmitter antagonists and effects of sacral neuromodulation in rats with chronically hyperactive bladder.
OBJECTIVE
To investigate to what extent antagonists of spinal neurotransmitters interact with the effects of sacral neuromodulation in a rat model of a chronically hyperactive urinary bladder.


METHODS
In female rats the urinary bladder was instilled with turpentine oil 2.5% to induce cystitis. After surviving for 10 days the rats were anaesthetized with urethane, the bladder catheterized and connected to a pressure transducer. Stimulating electrodes were placed in the sacral foramina bilaterally. The spinal cord was exposed by a laminectomy, and a small pool was placed on the cord for intrathecal administration of neurotransmitter antagonists. Sacral neuromodulation was applied before and after administering the antagonists. The antagonists used were: memantine, an antagonist for N-methyl-D-aspartate (NMDA) receptors; CNQX, an antagonist for non-NMDA receptors, and L-NAPNA, a blocker of nitric oxide synthase.


RESULTS
With no electrical neuromodulation, memantine and L-NAPNA abolished the cystitis-induced bladder contractions for approximately 4 and approximately 37 min, respectively. The effect of CNQX was similar to that of artificial cerebrospinal fluid. Electrical sacral modulation with no antagonists also transiently abolished the bladder contractions; at the highest intensity used, the pause was 2-3 min. Superfusion of the spinal cord with CNQX reduced this effect of neuromodulation significantly, whereas memantine had no influence, and L-NAPNA increased the neuromodulation-induced pause.


CONCLUSIONS
The results suggest that non-NMDA receptors are involved in the effects of sacral neuromodulation, whereas NMDA receptors appear to have no role. Nitric oxide is essential for maintaining the chronic hyperactive state of the urinary bladder.
Riazimand
Seyed-Hossein
SH
Institut für Anatomie und Zellbiologie III, Universität Heidelberg, Heidelberg, Germany.
Mense
Siegfried
S
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002908:Chronic Disease; D003556:Cystitis / Q000503:physiopathology; D004558:Electric Stimulation / Q000379:methods*; D005260:Female; D008160:Lumbosacral Plexus / Q000187:drug effects; D008559:Memantine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D014549:Urinary Incontinence / Q000209:etiology* / Q000503:physiopathology
D000813:Anilides; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C080840:N(G)-nitroarginine-4-nitroanilide; D001120:Arginine; D019001:Nitric Oxide Synthase; D008559:Memantine