Valsartan but not atenolol improves vascular pathology in diabetic Ren-2 rat retina

BACKGROUND: To determine whether angiotensin type 1 receptor blockade (AT1-RB) or antihypertensive therapy per se, attenuates acellular capillaries and proliferating endothelial cells in the retina of diabetic Ren-2 rats. METHODS: Eight-week-old hypertensive Ren-2 rats were made diabetic (streptozotocin, 55 mg/kg) or nondiabetic (0.1 mol/L citrate buffer) and studied for 20 weeks. Diabetic Ren-2 rats received by gavage the AT1-RB valsartan at 4, 10, or 40 mg/kg/d or the beta1-adrenergic receptor blocker atenolol at 30 mg/kg/d. Systolic blood pressure (BP) was measured every 4 weeks. Acellular capillaries (devoid of pericytes and endothelial cells) were counted on trypsin digests. Proliferating endothelial cells were evaluated using double immunolabeling for isolectin and proliferating cell nuclear antigen. RESULTS: Systolic BP was unchanged in control Ren-2 rats throughout the study (186.6 +/- 3.5 mm Hg, nondiabetic; 185.0 +/- 0.7 mm Hg, diabetic; week 20). In diabetic Ren-2 rats, 4 and 10 mg of valsartan and atenolol reduced systolic BP to a similar extent, and at 20 weeks were comparable to diabetic Sprague Dawley rats (123.0 +/- 1.4 mm Hg). In diabetic Ren-2 rats, 40 mg of valsartan reduced systolic BP (110.9 +/- 1.1 mm Hg, 20 weeks) below that of Sprague Dawley rats. Acellular capillaries and proliferating endothelial cells were increased by 3- and 1.6-fold, respectively, in diabetic Ren-2 controls and reduced with 4 and 10 mg of valsartan and further reduced with 40 mg of valsartan. Atenolol had no effect on retinal pathology in diabetic Ren-2 rats. CONCLUSIONS: Blockade of the renin-angiotensin system but not antihypertensive therapy with atenolol reduces vascular pathology in diabetic Ren-2 retina, suggesting that angiotensin II is a causative factor and therapeutic target in diabetic retinopathy.