The roles of small GTPases on urinary bladder of diabetic rats

The aim of this study was to investigate the roles of small GTPases RhoA and Rac1 on diabetic bladder dysfunction because of their role in the contraction of smooth muscle and urothelial function.In streptozotocin-induced diabetic rat model, control, diabetic, and insulin-treated diabetic groups were performed. Urinary bladder detrusor muscle strips were suspended in organ baths at the end of 8-10 weeks after streptozotocin injection. In the presence of Rho kinase inhibitor Y-27632 and/or Rac1 inhibitor NSC 23766, carbachol dose-response curves were obtained. Experiments were repeated in the presence of indomethacin for evaluation effects of prostaglandins which are released from urothelium. Diabetes-related histopathological changes and RhoA and Rac1 expressions were evaluated by hematoxilen ?eosin staining and by immunohistochemical staining respectively, in parafin-embedded sections of the urinary bladder.Carbachol produced dose-dependent contractile responses in all experimental groups. In diabetic and insulin-treated diabetic groups, contractile responses to CCh were higher than those of the control group. In presence of Y-27632, NSC 23766, and combination of Y-27632+NSC 23766, CCh-induced contractions were decreased significantly in all groups, inhibition in diabetic groups were significantly greater than those of the control groups. Insulin therapy didn?t improve the inhibitory effects of small GTPases in diabetic rats. Indomethacin significantly inhibited CCh-induced contractions in all groups, but there weren?t any significant differences among groups. Indomethacin didn?t potentiate the inhibitory effects of the small GTPases.In the histopathological evalution of bladder, wall thickness was increased in diabetic group compared to control group. There were no differences in RhoA immunreactivity among groups. The expressions of Rac1 were increased in all strata of urinary bladder in diabetic group compared to control group.In diabetic group, Rac1 expressions and the inhibition of CCh-induced contractions in the presence of Y-27632 and/or NSC 23766 were higher than those of the control group. Therefore small GTPases may play a role on bladder dysfunction in diabetes. At this point further studies are needed for promising therapies that target the small GTPases on diabetic bladder dysfunction in diabetes.