Modulation of retinal blood flow by kinin B1 receptor in Streptozotocin-diabetic rats

The vasoactive kinin B1 receptor (B1R) is overexpressed in the retina of diabetic rats in response to hyperglycemia and oxidative stress. The aim of the present study was to determine whether B1R could contribute to the early retinal blood flow changes occurring in diabetes. Male Wistar rats were rendered diabetic with a single i.p. injection of Streptozotocin (STZ) and studied 4 days or 6 weeks after diabetes induction. The presence of B1R in the retina was confirmed by Western blot. The impact of oral administration of the B1R selective antagonist SSR240612 (10 mg/kg) was measured on alteration of retinal perfusion in awake diabetic rats by quantitative autoradiography. Data showed that B1R was upregulated in the STZ-diabetic retina at 4 days and 6 weeks. Retinal blood flow was not altered in 4-day diabetic rats compared with age-matched controls but was significantly decreased following SSR240612 treatment. In 6-week diabetic rats, retinal blood flow was markedly reduced compared to control rats and SSR240612 did not further decrease the blood flow. These results suggest that B1R is upregulated in STZ-diabetic retina and has a protective compensatory role on retinal microcirculation at 4 days but not at 6 weeks following diabetes induction.

► RBF is not changed in 4-day diabetic rats but decreased at 6 weeks.
► Kinin B1 receptor is overexpressed in the retina of 4-day and 6-week diabetic rats.
► Kinin B1 receptor antagonist decreases RBF in 4-day diabetic rats.
► Kinin B1 receptor antagonist had no effect on RBF in 6-week diabetic rats.
► Kinin B1 receptor may have a protective effect to reduce RBF deficit in 4-day diabetic rats.