Effect of Nicorandil on Retinal Microcirculation in Streptozotocin–Induced Diabetic Rats

Abstract

Abstract: : Purpose:To evaluate the effect of nicorandil, which is reported to act as an ATP–sensitive K+ channel opener and nitric oxide donor, on the retinal microcirculation in streptozotocin (STZ)–induced diabetic rats. Methods: Diabetic Brown–Norway rats were made by a single intravenous injection of STZ (Sigma; 65mg/kg). Diabetes was confirmed by a blood glucose level above 350 mg/dl 48 hrs after STZ administration. Rats were divided as follows: untreated diabetic group (n=5), nicorandil–treated group (chow containing 0.003% nicorandil) diabetic group (n=5), and a nondiabetic control group (n=5). Four weeks later, retinal microcirculation was evaluated by acridine orange leukocyte digital fluorography using laser scanning ophthalmoscopy. Dye–stained leukocytes trapped in the retina (retinal leukostasis) were counted within the area around the optic disc (6 disc diameter) and compared between each group. Results: Retinal leukostasis in the untreated diabetic group (93.2±27.1cells) was significantly higher than in nondiabetic controls (21.3±2.3cells,P <0.05)and nicorandil reversed the leukostasis enhanced by diabetes (18.4±11.3cells,P <0.05). Conclusions: Nicorandil prevented development of retinal leukostasis in STZ–induced diabetic rats, suggesting that it has therapeutic efficacy in early diabetic retinopathy.

Keywords: nitric oxide • diabetic retinopathy • cell adhesions/cell junctions