EFFECTS OF DIABETES MELLITUS ON THE BIOMECHANICAL PROPERTIES AND PHARMACOLOGICAL FUNCTION OF THE FEMALE RAT URETHRA EX-VIVO
Rachelle Lynn Prantil, MS
University of Pittsburgh, 2004
Diabetic cystopathy results in a grossly distended, hypomotile bladder due to inefficient voiding. While the bladder has been extensively studied, little effort has been made towards the understanding of the urethra and the effects of this devastating disease. The current study is aimed to evaluate the effects of diabetes mellitus (DM) on the biomechanical properties and the pharmacological function of the female rat urethra ex vivo.
DM was induced in female rats by injection of streptozotocin. At 3, 5,and 10 weeks, the urethras were excised and mounted into an ex-vivo system at in vivo length. For mechanical testing, urethras were subjected to stepwise increases of static, intraurethral pressure from 0 to 20 mmHg in both a baseline and passive state. Continuous outer diameter measurements were made using a laser micrometer at proximal, middle, and distal portions of the urethra. Compliance and beta stiffness were calculated from measured data. Pharmacological experiments involved assessments of mid urethral outer diameter response to Nç Nitro-L-arginine, phenylephrine, and EDTA. Age matched normal urethras served as controls. Statistical comparisons were made via ANOVA. Tissue was then processed for immuno- and histochemical quantification of smooth muscle, collagen, and elastin.
For baseline healthy tissue, results showed a proximal to distal compliance gradient (proximal most compliant and distal least compliant), and the passive state enhanced the observation. Baseline beta stiffness values showed an increased stiffness in proximal and middle urethral portions by 5 and 10 weeks, and baseline compliance values showed at low pressures showed an increase in proximal compliance at 3 weeks and a decrease in proximal compliance at 5 weeks at high pressures. Passive beta stiffness and compliance values indicated proximal urethral stiffening by 10 weeks DM. Pharmacological studies revealed that DM abolishes endogenous nitric oxide release and increases the time to reach maximal relaxation. In cases of severe DM, alpha 1 adrenergic contraction was minimized. Little or no differences were found in the amount collagen, smooth muscle, and elastin.
From these findings, it can be concluded that DM causes urethral stiffening and impaired contractile and relaxation urethral mechanism. Damaged urethral properties and function have serious implications for outlet resistance; thus, contributing to diabetic cystopathy.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04132004-013008 |
| Date | 09 June 2004 |
| Creators | Prantil, Rachelle Lynn |
| Contributors | William C. de Groat, Ph.D., Richard E. Debski, Ph.D., David A. Vorp, Ph.D., Harvey S. Borovetz, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04132004-013008/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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