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

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.

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.

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.

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.