Ultrastructural alterations in capillaries of the diabetic hypertensive rat retina: protective effects of ACE inhibition.

Aims/hypothesis: The ACE inhibitor cilazapril was administered to diabetic hypertensive rats to evaluate its ability to influence the development of retinal capillary alterations.

Methods: Normotensive (strain: Wistar Kyoto) and genetically hypertensive (strain: spontaneously hypertensive) rats were rendered diabetic by intravenous injections of streptozotocin. Half of the diabetic animals received cilazapril with their daily food. At 20 weeks of diabetes, endothelial cells, pericytes and extracellular matrix were assessed by ultrastructural morphometry. Each experimental group consisted of seven animals.

Results: Cilazapril normalised systolic arterial pressure in diabetic hypertensive rats (137+/-2 mm Hg compared with 188+/-16 mm Hg in non-medicated diabetic hypertensive rats, p<0.001). The number of endothelial intercellular junctions was reduced in untreated diabetic hypertensive rats (0.15+/-0.05, p<0.02, vs 0.47+/-0.20 in non-diabetic normotensive rats). In diabetic hypertensive animals treated with cilazapril, this loss was attenuated (0.32+/-0.16, p<0.05). The significant thickening of the basement membrane observed in the diabetic normotensive (132.8+/-19.4 nm) and diabetic hypertensive (150.3+/-20.2 nm) groups was decreased by cilazapril in the diabetic hypertensive group (116.7+/-11.0 nm, p<0.01), but was unaffected in the normotensive (131.9+/-17.3 nm) group. No protective effect of the drug was observed in either group on pericytes.

Conclusions/interpretation: Long-term administration of an effective antihypertensive therapy normalises endothelial alterations and basement membrane thickness in diabetic hypertensive conditions, and thus may account for the well-known improvement of the blood-retinal barrier observed during antihypertensive treatment.