Characteristics of Lower Urinary Tract Dysfunction and Bladder Afferent Nerve Properties in Type 2 Diabetic Goto-Kakizaki Rats

Abstract

We investigated longitudinal changes in lower urinary tract function, especially sensory function, in the type 2 diabetes mellitus model of Goto-Kakizaki rats. We used 16 Wistar and 16 Goto-Kakizaki rats. Body weight, blood glucose, 24-hour voiding frequency-volume data and cardiovascular system data were measured every 3 weeks starting at age 5 weeks until age 14 weeks and then every 6 weeks until age 44 weeks. At ages 10 and 46 weeks conscious cystometry was done, pelvic afferent nerve fiber conduction velocity was measured using urethane anesthesia and isolated detrusor smooth muscle function was determined. Goto-Kakizaki rats showed lower body weight, higher blood glucose and mean voided volume, and less voiding frequency than Wistar rats throughout the observation period. In 46-week-old Goto-Kakizaki rats lower peak micturition pressure, larger bladder capacity and higher bladder compliance were noted on cystometry, while slower conduction velocity and a lesser proportion of Aδ fibers were observed on conduction velocity measurement. Goto-Kakizaki rats showed a lower contractile response to carbachol but not to electrical field stimulation or high K(+) in isolated detrusor smooth muscle. These differences between the 2 groups of rats at age 46 weeks were not noted at age 10 weeks. Cardiovascular system results did not differ between the 2 groups. The results of this longitudinal study in Goto-Kakizaki rats indicate that type 2 diabetes induces bladder sensory dysfunction, manifesting as slower bladder afferent conduction velocity, larger bladder capacity and greater hypocontractility to acetylcholine.