Dosso A A, Rungger-Brändle E, Leuenberger P M
Laboratory of Cell Biology, University Eye Clinic, Geneva, Switzerland.
Clinique d'Ophtalmologie, Hôpital cantonal universitaire, 22, rue Alcide Jentzer, 1211, Genève 14, Switzerland.
Diabetologia. 2004 Jul;47(7):1196-1201. doi: 10.1007/s00125-004-1442-3. Epub 2004 Jul 9.
AIMS/HYPOTHESIS: The ACE inhibitor cilazapril was administered to diabetic hypertensive rats to evaluate its ability to influence the development of retinal capillary alterations.
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.
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.
目的/假设：对糖尿病高血压大鼠给予血管紧张素转换酶（ACE）抑制剂西拉普利，以评估其影响视网膜毛细血管病变发展的能力。
通过静脉注射链脲佐菌素使正常血压（品系：Wistar Kyoto）和遗传性高血压（品系：自发性高血压）大鼠患糖尿病。一半糖尿病动物在日常食物中添加西拉普利。糖尿病20周时，通过超微结构形态测量法评估内皮细胞、周细胞和细胞外基质。每个实验组有7只动物。
西拉普利使糖尿病高血压大鼠的收缩压恢复正常（137±2 mmHg，未用药的糖尿病高血压大鼠为188±16 mmHg，p<0.001）。未治疗的糖尿病高血压大鼠内皮细胞间连接数量减少（0.15±0.05，p<0.02，非糖尿病正常血压大鼠为0.47±0.20）。在用西拉普利治疗的糖尿病高血压动物中，这种减少得到缓解（0.32±0.16，p<0.05）。糖尿病正常血压组（132.8±19.4 nm）和糖尿病高血压组（150.3±20.2 nm）中观察到的基底膜显著增厚，在糖尿病高血压组中被西拉普利降低（116.7±11.0 nm，p<0.01），但在正常血压组（131.9±17.3 nm）中未受影响。在两组中均未观察到该药物对周细胞有保护作用。
结论/解读：长期给予有效的抗高血压治疗可使糖尿病高血压状态下的内皮改变和基底膜厚度恢复正常，因此可能解释了在抗高血压治疗期间观察到的血视网膜屏障的显著改善。
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