The Significance of Periurethral Fibrosis and the Change of Nitric Oxide Synthase Containing Nerves in the Urethra of Diabetic Rats / 대한비뇨기과학회지

PURPOSE: We have previously demonstrated that increased urethral resistance was more prominent in diabetic rats than in controls. This may result from a compressive obstruction such as damage of the urethral nerve containing nitric oxide. Another possible cause for urethral obstruction could be a constrictive obstruction such as a periurethral fibrosis. In the present study, we investigated the changes in the expression of nitric oxide synthase(NOS) isoforms(compressive obstruction) and collagen subtypes (constrictive obstruction) in the urethral tissues of non-insulin dependent diabetic rats. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats(18 diabetic rats and 18 control rats), bred from birth, were included in this study. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin(90mg/kg) on the second day after birth. Urethral tissues were harvested at 12, 24 and 36 weeks after induction of diabetes and were stained for neuronal NOS(nNOS) and Masson trichrome. We also performed reverse transcriptase-polymerase chain reaction or Western blot analysis to evaluate mRNA or protein expression of NOS isoforms and collagen subtypes in the urethral tissues. RESULTS: Immunohistochemical staining and Western blot analysis of nNOS revealed that the immunoreactivity and nNOS expression in the urethra was lower in the diabetic rats than in the controls. The Masson trichrome staining showed that there was urethral fibrosis in the diabetic rats. The mRNA or protein expression of collagen subtypes, especially type I collagen, were higher in the diabetic rat urethra than in the controls. CONCLUSIONS: These data suggest that the increased urethral resistance in diabetic rats may be attributable to a decrease in the urethral nNOS expression and an increase in collagen content. Urethral dysfunction as well as a cystopathy may play an important role in the pathogenesis of diabetes- induced voiding dysfunction. (Korean J Urol 2007;48:1050-1057)

Urethral Dysfunction in a Non-Insulin Dependent Diabetes Mellitus Rat Model / 대한비뇨기과학회지

Purpose: We assessed whether urethral dysfunction related to nitric oxide (NO) is responsible for voiding dysfunction in rats with non-insulin dependent diabetes mellitus. Materials and Methods: A total of 27 male Sprague-Dawley rats (14 diabetic rats and 13 control rats) were included. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin (90mg/kg) on the second day after birth. Cystometry with determining the detrusor leak point pressure (LPP) was performed in the diabetic and control rats at the age of 12 and 24 weeks. The effect of intravenous injection with L- nitro-arginine-methyl ester (L-NAME) as a NO inhibitor and sodium nitroprusside (SNP) as a NO donor were also evaluated. Results: Diabetic rats showed an increased bladder capacity and a higher detrusor LPP than the controls at both ages. After intravenous injection of L-NAME, the control rats showed an increased detrusor LPP, but no change was observed in the diabetic rats. With administering SNP, the detrusor LPP was decreased in both the diabetic and control rats. Conclusions: Urethral resistance was more increased in the diabetic rats than the controls, which may be the result of dysfunction of the urethral nerve containing NO. The urethral factor, in addition to cystopathy, also plays an important role for the pathogenesis of voiding dysfunction in diabetic patients.