Urethral dysfunction in diabetic rats.
PURPOSE: We investigated the effects of diabetes mellitus (DM) on urethral relaxation mechanisms during reflex bladder contractions in rats. MATERIALS AND 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, K; Fraser, MO; Hirao, Y; De Groat, WC; Chancellor, MB; Yoshimura, N
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