INVESTIGATIVE UROLOGY

Urethral dysfunction in diabetic rats
Torimoto K, Fraser MO, Hirao Y, De Groat WC, Chancellor MB, Yoshimura N
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
J Urol. 2004; 171: 1959-64

• 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 intravesically), 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 intravesically), 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.
  
  
• Editorial Comment
  Cystopathy characterized by high post-void residual urine volume, weaken bladder sensations and diminished bladder contractility affects around 80% of patients with noninsulin dependent diabetes mellitus. However, as yet, little is known on the effects of diabetes mellitus on urethral function.
  Previous studies showed that nitric oxide is the most important transmitter that induces urethral relaxation during voiding. It has also been demonstrated that relaxation responses to nitric oxide in urethral muscle strips were decreased in diabetic rabbits. Thus, the authors investigated if urethral relaxation during the voiding reflex would be decreased in diabetes mellitus. In addition, the authors evaluated the effects on diabetes mellitus induced urethral dysfunction of L-arginine treatment, a drug that can increase endogenous nitric oxide production.
  The authors found that relaxation mechanisms of urethral striated and smooth muscle during reflex bladder contractions are impaired in diabetes mellitus. They proposed that this defect coupled with bladder hypoactivity could result in inefficient voiding and bladder overdistention in diabetes mellitus. The authors also proposed that therapy with L-arginine might be useful for partially restoring the urethral relaxation mechanism in diabetes mellitus.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil