Effects of MK-801 on bladder overactivity in rats with cerebral infarction.
OBJECTIVE
Our objective was to evaluate the underlying mechanisms of neurogenic voiding dysfunction following cerebral infarction.


METHODS
The left middle cerebral artery (MCA) was occluded using 4-0 monofilament nylon thread in male S-D rats. Cystometric examination was performed in unanesthetized and urethane-anesthetized rats through a catheter chronically implanted in the dome of the bladder.


RESULTS
Bladder capacity of unanesthetized or urethane anesthetized rats was significantly reduced just after occlusion of the left MCA; 2 weeks after the occlusion, the capacity was less than half that in sham-operated rats. Intravenous administration of N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 to the unanesthetized sham-operated rats led to a marked dose-dependent decrease in bladder capacity. Its administration to unanesthetized rats with cerebral infarction resulted in a slight decrease in bladder capacity. In the urethane-anesthetized state, the bladder capacity of the rats with cerebral infarction was significantly increased by MK-801, 0.1 mg./kg., without inhibiting the contraction pressure or increasing the amount of residual urine. A high dose (1 mg./kg.) of MK-801 was required to increase the bladder capacity of sham-operated rats. This led to an inhibition of contraction pressure and an increase in residual urine.


CONCLUSIONS
Results in urethane anesthetized rats indicate that NMDA glutamatergic transmission is important in the overactivity of the bladder following a cerebral infarction. This model is useful in studying the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.
Yokoyama
O
O
Department of Urology, School of Medicine, Kanazawa University, Katsuyama, Japan.
Ishiura
Y
Y
Komatsu
K
K
Mita
E
E
Nakamura
Y
Y
Kunimi
K
K
Morikawa
K
K
Namiki
M
M
D000758:Anesthesia; D000818:Animals; D002544:Cerebral Infarction / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology*; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology*
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate