Korean J Urol KJU Korean Journal of Urology 0494-4747 The Korean Urological Association 10.4111/kju.2006.47.9.1007 Original Article Urethral Dysfunction in a Non-Insulin Dependent Diabetes Mellitus Rat Model Chung Jae-Seung Yoo Hyung Sang http://orcid.org/0000-0001-8508-9099 Lee Tack Department of Urology, Inha University College of Medicine, Incheon, Korea. Corresponding author (lt11@inha.ac.kr) 09 2006 30 09 2006 47 9 1007 1012 13 06 2006 05 07 2006 Copyright © 2006 The Korean Urological Association 2006 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.

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Diagrammatic representation for defining the parameter (detrusor LPP) and the findings of cystometry. The upper part is the pressure tracing in the bladder and the lower is that in the urethra. The detrusor LPP is measured by the bladder pressure at which the stable urethral pressure abruptly rises. The findings are without medication (A), premedicated with L-NAME (B) and with sodium nitroprusside (C). LPP: leak point pressure.

Trends of the glucose levels in diabetes-induced rats (the NIDDM model). Transient hyperglycemia rapidly developed that this lasted for 2-4 days. The plasma glucose concentrations remained at near normal levels until about 6 weeks of age, whereupon frank chronic hyperglycemia developed with plasma glucose concentrations that usually ranged between 200-500mg/dl.

Numbers of rats used in experiments

*Urodynamic study with pre-injection of L-Nω-nitro-L-arginine methyl ester (L-NAME), †Urodynamic study with injection of sodium nitroprusside (SNP), which was done one hour after experiment with L-NAME

The bladder capacity in normal and diabetic rats according to the age

The capacities of diabetes mellitus (DM) rats were significantly increased than control rats: *p<0.05, †p<0.01 Student's t-test (unpaired)

The detrusor leak point pressure in normal and diabetic rats with/without medication according to the age

Results are expressed as mean±standard error of the mean (cmH2O). Comparisons were made for the leak point pressures (LPP) between the control and diabetic rats: *p<0.05, †p<0.01 Student's t-test (unpaired), versus LPPs without medication: ‡p<0.05, §p<0.01 Student's t-test (paired), ∥Detrusor leak point pressure with pre-injection of L-NAME, Detrusor leak point pressure with injection of sodium nitroprusside