EFFECTS OF DIABETES MELLITUS ON THE BIOMECHANICAL PROPERTIES AND PHARMACOLOGICAL FUNCTION OF THE FEMALE RAT URETHRA EX-VIVO

EFFECTS OF DIABETES MELLITUS ON THE BIOMECHANICAL PROPERTIES AND PHARMACOLOGICAL FUNCTION OF THE FEMALE RAT URETHRA EX-VIVORachelle Lynn Prantil, MSUniversity of Pittsburgh, 2004Diabetic 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 Nč 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