Urethral dysfunction in diabetic rats.
OBJECTIVE
We investigated the effects of diabetes mellitus (DM) on urethral relaxation mechanisms during reflex bladder contractions in rats.


METHODS
Five weeks after streptozotocin injection (65 mg/kg intraperitoneally) the effects of DM on urethral relaxation mechanisms were evaluated by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) using urethane anesthesia.


RESULTS
In diabetic rats the UPP nadir during urethral relaxation and intravesical pressure thresholds for inducing urethral relaxation were significantly higher (199% and 92%, respectively) than in normal rats, while baseline UPPs were not significantly different. The mean rate and amplitude of high frequency oscillations of urethral striated muscle in diabetic rats were also significantly lower (17% and 64%, respectively) compared with normal rats. Following alpha-bungarotoxin treatment to eliminate striated muscle sphincter contractions intravenous administration of L-arginine (200 mg/kg) [corrected] , the substrate of nitric oxide (NO) synthase, decreased the UPP nadir (36% and 22%, in diabetic and normal rats) as well as intravesical pressure thresholds (49% and 22%, respectively). The effect was greater (61% to 126%) in diabetic rats than in normal rats. In each group of rats the effect of L-arginine was inhibited by Nomega-nitro-L-arginine (100 mg/kg intravenously) [corrected], a NO synthase inhibitor.


CONCLUSIONS
During reflex bladder contractions streptozotocin induced diabetic rats exhibited smooth and striated muscle dysfunctions of the urethral outlet. L-arginine therapy, which could augment urethral smooth muscle relaxation by increasing NO production, may be useful for partially restoring the urethral relaxation mechanism in DM.
Torimoto
Kazumasa
K
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213-3221, USA.
Fraser
Matthew O
MO
Hirao
Yoshihiko
Y
De Groat
William C
WC
Chancellor
Michael B
MB
Yoshimura
Naoki
N
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014521:Urethra / Q000187:drug effects / Q000503:physiopathology*