Influences of external urethral sphincter relaxation induced by alpha-bungarotoxin, a neuromuscular junction blocking agent, on voiding dysfunction in the rat with spinal cord injury.
OBJECTIVE
To determine whether external urethral sphincter (EUS) relaxation induced by alpha-bungarotoxin, a highly selective neuromuscular junction blocking agent, could ameliorate voiding dysfunction after spinal cord injury (SCI) in rats.


METHODS
The effects of intravenous alpha-bungarotoxin (333 microg/kg) were evaluated during cystometry in decerebrate, unanesthetized female Sprague-Dawley rats (250 to 300 g) with spinal cords chronically transected at T7-9 (n = 7) or with normal spinal cords (NSC) (n = 7). Parameters measured included voided volume (VV), residual volume (RV), volume threshold for inducing micturition (VT), voiding efficiency (VE), micturition pressure (MP), pressure threshold for inducing micturition (PT), bladder contraction duration (BCD), and compliance (CP).


RESULTS
In SCI rats, treatment with alpha-bungarotoxin improved voiding. The toxin increased VE (31%) and reduced RV (42%), MP (52%), BCD (14%), and VT (31%). VV, PT, and CP were not altered. In NSC rats, alpha-bungarotoxin decreased VE (23%), increased RV (63%), and decreased MP (36%), VV (38%), and VT (20%) but did not change BCD and CP.


CONCLUSIONS
The results of our study demonstrated that alpha-bungarotoxin improved voiding in SCI rats by reducing urethral outlet resistance. However, in NSC rats, the toxin reduced voiding, probably by suppressing high-frequency phasic sphincter activity, necessary for efficient urine elimination in normal animals. The present results provide further support for the view that drugs that depress striated muscle activity can be useful in the treatment of voiding dysfunction after SCI.
Yoshiyama
M
M
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
deGroat
W C
WC
Fraser
M O
MO
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D009126:Muscle Relaxation / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications; D014521:Urethra / Q000187:drug effects*; D014555:Urination Disorders / Q000188:drug therapy / Q000209:etiology
D002038:Bungarotoxins; D009466:Neuromuscular Blocking Agents