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

Exp Eye Res. 2011 Jun;92(6):482-9. doi: 10.1016/j.exer.2011.03.007. Epub 2011 Mar 21.

Abstract

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 (10mg/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Blood Flow Velocity
  • Blotting, Western
  • Bradykinin B1 Receptor Antagonists
  • Cerebrovascular Circulation / physiology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / physiopathology*
  • Dioxoles / pharmacology
  • Fluorescein Angiography
  • Male
  • Rats
  • Rats, Wistar
  • Receptor, Bradykinin B1 / metabolism*
  • Regional Blood Flow / physiology*
  • Retinal Vessels / physiology*
  • Sulfonamides / pharmacology
  • Up-Regulation

Substances

  • 2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide
  • Bradykinin B1 Receptor Antagonists
  • Dioxoles
  • Receptor, Bradykinin B1
  • Sulfonamides