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Jae-Seung Chung, Hyung Sang Yoo, Tack Lee
Abstract
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.
Figures and Tables
Fig. 1
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.
Fig. 2
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.
Table 3
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
References
1. Frimodt-Moller C. Diabetic cystopathy: epidemiology and related disorders. Ann Intern Med. 1980. 92:318–321.
2. Vinik AI, Holland MT, Le Bear JM, Liuzze FJ, Stansberry KB, Colen LB. Diabetic neuropathies. Diabetes Care. 1992. 15:1926–1975.
3. Motzkin D. The significance of deficient bladder sensation. J Urol. 1968. 100:445–450.
4. Shin YG, Park YL, Cho SR. Comparison of medical therapeutic efficacy in the patient with diabetic cystopathy according to prevalence period of diabetes mellitus. Korean J Urol. 2002. 43:131–134.
5. Choi AR, Lee SJ, Lee JY. Urodynamic evaluations according to clinical findings and clinical significance of glycosylated hemoglobin (HbA1C) in patients with diabetic cystopathy. Korean J Urol. 2002. 43:1029–1034.
6. Michel MC, Mehlburger L, Schumacher H, Bressel HU, Goepel M. Effect of diabetes on lower urinary tract symptoms in patients with benign prostatic hyperplasia. J Urol. 2000. 163:1725–1729.
7. Hwang ST, Oh MH, Yang SK. Usefulness of urodynamic study in diabetic cystopathy. Korean J Urol. 1997. 38:185–191.
8. Mumtaz FH, Khan MA, Thompson CS, Morgan RJ, Mikhailidis DP. Nitric oxide in the lower urinary tract: physiological and pathological implications. BJU Int. 2000. 85:567–578.
9. Torimoto K, Fraser MO, Hirao Y, De Groat WC, Chancellor MB, Yoshimura N. Urethral dysfunction in diabetic rats. J Urol. 2004. 171:1959–1964.
10. Ozturk Y, Altan VM, Yildizoglu-Ari N. Effects of experimental diabetes and insulin on smooth muscle functions. Pharmacol Rev. 1996. 48:69–112.
11. Weir GC, Clore ET, Zmachinski CJ, Bonner-Weir S. Islet secretion in a new experimental model for non-insulin-dependent diabetes. Diabetes. 1981. 30:590–595.
12. Ellenberg M. Development of urinary bladder dysfunction in diabetes mellitus. Ann Intern Med. 1980. 92:321–323.
13. Eika B, Levin RM, Longhurst PA. Collagen and bladder function in streptozotocin-diabetic rats: effect of insulin and aminoguanidine. J Urol. 1992. 148:167–172.
14. Koo HP, Santarosa RP, Buttyan R, Shabsigh R, Olsson CA, Kaplan SA. Early molecular changes associated with streptozotocin-induced diabetic bladder hypertrophy in the rat. Urol Res. 1993. 21:375–381.
15. Hellweg R, Hartung HD. Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy. J Neurosci Res. 1990. 26:258–267.
16. Kim JC, Seo SL, Park YH, Hwang TK. Changes of detrusor contractility and growth factors in streptozotocin-induced NIDDM rat. Korean J Urol. 2000. 41:615–621.
17. Andersen JT, Bradley WE. Abnormalities of bladder innervation in diabetes mellitus. Urology. 1976. 7:442–448.
18. Norlen LJ, Blaivas JG. Unsuspected proximal urethral obstruction in young and middle-aged men. J Urol. 1986. 135:972–976.
19. Staskin DR. Hydroureteronephrosis after spinal cord injury. Effects of lower urinary tract dysfunction on upper tract anatomy. Urol Clin North Am. 1991. 18:309–316.
20. McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of urodynamic testing in myelodysplastic patients. J Urol. 1981. 126:205–209.
21. O'Connell HE, McGuire EJ. Susie B, Deichmann C, Masthay C, editors. Leak point pressures. Urinary incontinence. 1992. St Louis: Mosby;93–98.
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