Increased numbers of caveolae in retinal endothelium and pericytes in hypertensive diabetic rats

Purpose Long-term clinical studies have now shown that tight control of blo od pressure in type 2 diabetes reduces the risk of diabetes-related death a nd common diabetic complications, including diabetic retinopathy. However, the mechanisms by which hypertension enhances diabetic microvascular diseas e, especially diabetic retinopathy, are poorly understood. We developed an experimental model of hypertension in diabetic rats and studied the early u ltrastructural changes in retinal capillaries under these conditions. Methods Hypertension was induced in diabetic BioBreeding (BB) rats by unila teral nephrectomy, weekly subcutaneous mineralocorticoid and 0.9% oral sali ne. Serial blood pressures and ultrastructural features of retinal capillar ies were recorded in four groups: normotensive Wistar rats, normotensive di abetic rats, hypertensive Wistar rats and hypertensive diabetic rats. Results A significant and sustained increase in systolic blood pressure occ urred in both groups of nephrectomised rats. There was a significant increa se in the number of caveolae (i) in both pericytes and endothelial cells in animals with hypertension and diabetes together compared with all other gr oups and (ii) in pericytes in animals with diabetes alone. The number of di rect contacts between pericytes and endothelial cells was reduced in diabet ic and hypertensive diabetic animals. Hypertension and diabetes had an inte ractive effect in producing retinal capillary basement membrane thickening. Conclusions In the BE rat hypertension and diabetes have an interactive eff ect in increasing the number of caveolae in both endothelial cells and peri cytes. We speculate that this may be a reflection of changes in calcium and nitric oxide metabolism in these animals.