International Journal of Urology (2005) 12, 677–682 Blackwell Science, LtdOxford, UKIJUInternational Journal of Urology0919-81722005 Blackwell Publishing Asia Pty LtdJune 2005126677682Original Article Effects of urothelium on bladder contractilityM Kosan et al. Correspondence: Murat Kosan MD, Sokollu Cad. Seftali Sok. No:68/6, 06460 Dikmen, Ankara, Turkey. Email: drmkosan@lycos.com Received 2 February 2004; accepted 16 December 2004. Original Article Effect of urothelium on bladder contractility in diabetic rats MURAT KOSAN, 1 GAYE HAFEZ, 2 BÜLENT ÖZTÜRK, 1 OZAN ÖZGÜNES, 2 SERAP GÜR 2 AND MESUT ÇETINKAYA 1 1 Second Urology Clinic, Ankara Numune Education and Research Hospital, and 2 Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey Abstract Aim: It is known that physiopathological changes in diabetes affect the function of the bladder. In this study, we aimed to demonstrate the possible effects of diabetes on the urothelium during this physiopathological process. Methods: Diabetes was induced in rats by tail vein injection of 35 mg/kg streptozotocin. Eight weeks later, intact and denuded bladder strips were prepared from these rats. Electrical field stimulation (EFS; 0.5–32 Hz), carbachol (10 -8 -10 -3 mol/L; cumulative dosage-response curves) and KCl (120 mmol/L) were used for the evaluation of the contractile responses. All responses were expressed as mg tension developed per mg of bladder tissue. Weights of rats and of their bladders, blood glucose levels, and frequency- and concentration–response curves were compared using ANOVA, the paired t-test and the independent t-test. Differences were considered significant at P < 0.05. Results: Although no differences related to the weight of bladders of the control and diabetic groups were observed, there were differences in blood glucose levels and body weights between the two groups. Similarly, although there were no differences between the data obtained with EFS and KCl from tissues with intact and denuded strips in the control group, carbachol responses significantly differed between intact and denuded strips in the non-diabetic group. These differences were not observed in the diabetic group. In the control groups, in the presence of additional strips with intact urothelium placed in the medium containing denuded tissue, the differences in contractile responses between the intact control strip and the denuded strip disappeared. Conclusions: Diabetes possibly changes the interaction between the relaxant factors that are released from urothelium and muscarinic stimulation, but these interactions are not completely understood yet. Consequently, the response of the bladder to contractile stimulants is also affected. Further studies are required to reveal the mechanism by which diabetes influences the urothelium. Key words contractility, diabetes, rat, urinary bladder, urothelium. Introduction The detrusor is rich in cholinergic innervation and mus- carinic receptors. 1 The urothelium is also rich in inner- vation and muscarinic receptors. 2 The urothelium plays an important role in the filling and distension mecha- nisms of the bladder, probably because of these properties. It has been shown in previous studies that removal of the urothelium causes significant increases in the con- tractile responses of the detrusor. 3–5 It has been proposed that an inhibitor factor released after the stimulation of muscarinic receptors could be responsible for this effect. 4 However, the mechanism of this effect has not been fully revealed yet because of its complex nature. It has been found that placing a second tissue strip with intact urothelium into the organ bath inhibited the increase in the observed contractile response. 3 It has also been reported that the inhibitory factor originating from the urothelium does not have an effect via nitric oxide (NO) and cyclooxygenase, or via catecholamines,