Angiotensin II Mediates Retinal Leukostasis in Diabetic Rats

Abstract

Abstract: : Purpose:To determine whether suppressing the activity of the endogenous renin angiotensin system affects diabetic retinal leukostasis. Methods:Rats with streptozotocin-induced diabetes (6-8/group, glycemia ≥250 mg/dl,) were treated with an ACE inhibitor (ramipril) or with an Angiotensin II AT₁ receptor antagonist (losartan). We also tested the effect of a Ca channel blocker, Nifedipine. Two weeks after diabetes induction, the rats were examined for retinal leukostasis using a scanning laser ophthalmoscope. Leukocytes were labeled with acridine orange. Dextran- fluorescein was used to define the relationship of static leukocytes with the retinal microcirculation. Arrested leukocytes were defined as cells that were observed static in the retina for at least 3 min. Leukocyte-induced capillary non-perfusion was defined as capillaries that show no perfusion for at least 2 min, apparently due to a trapped static leukocyte. Leukostasis was expressed as 10^-5cells/pixels^2. Results:Retinal leukostasis was markedly higher in diabetic rats compared with normal controls: 4.4±0.5 vs. 0.13±0.08; p< 0.05. Treatment with either ramipril or losartan significantly decreased leukostasis: 1.4±0.16 and 1.3±0.14 respectively; p< 0.05 vs. untreated diabetic rats. Leukocyte-induced capillary nonperfusion was not observed in normal control rats. It was 0.75±0.26 in untreated diabetic rats, and it was significantly decreased in rats treated with either ramipril or losartan: 0.18±0.18 and 0.15±0.29 respectively; p< 0.05 vs untreated. Nifedipine treatment did not result in significant changes in either retinal leukostasis or capillary nonperfusion. All treatments induced similar (~16 mm Hg) decreases in systolic blood pressure. Conclusions: Suppressing the activity of the endogenous renin angiotensin system markedly decreases the retinal leukostasis and capillary nonperfusion that occurs after the onset of type I diabetes in rats. These effects are not dependent on blood pressure changes. Angiotensin II may mediate retinal leukostasis in early diabetes.

Keywords: diabetic retinopathy • retina • diabetes