Cerebral Endothelial Dysfunction in Diabetes: Intravital Microscopic Analysis Using Streptozotocin-induced Diabetic Rats

Endothelial function of cerebral microvessel in diabetes was evaluated using streptozotocin (STZ)-induced diabetic rats (blood glucose of >/=300 mg/dl). At 36 weeks after STZ injection, the rats were anesthetized with sodium pentobarbital. The cerebral microcirculation in control and STZ groups was directly observed, using intravital fluorescence videomicroscopy. To evaluate the endothelial function in vivo, the number of leukocytes adhering to postcapillary venules were counted, and cerebral arteriolar responses to acetylcholine (ACh) and nitroglycerine (NTG) were examined. The results showed that the leukocyte adhesion to cerebral postcapillary venular endothelium increased significantly in STZ-rats, compared with control rats. The vasodilatory responses of cerebral arterioles (20-30 microm) to ACh decreased significantly in STZ-rats, compared with control rats (p<0.01), but the responses to NTG did not alter in diabetes. These results indicate that the impaired responses should occur on the endothelial cell. In conclusion, endothelial dysfunction induced in diabetes are characterized by impaired endothelium-dependent vasodilation and increased leukocyte adhesion to endothelial cells.