Attenuation of diabetes-induced retinal vasoconstriction by a thromboxane receptor antagonist

Exp Eye Res. 2009 Jan;88(1):106-12. doi: 10.1016/j.exer.2008.10.008. Epub 2008 Nov 1.

Abstract

Retinal blood flow has been reported to decrease early in human diabetes as well as in diabetic animal models. The purpose of the present study is to investigate the role of thromboxane receptor binding in the decrease of flow. C57BL/6 mice were injected with streptozotocin (STZ) at 11-12 weeks of age and remained hyperglycemic for 4 weeks. The mice were treated with a selective thromboxane receptor antagonist, GR32191B (vapiprost), in drinking water for the final three weeks at a dose of 1mg/kg/day. In separate experiments, vapiprost was administered only once, as an acute injection 25min prior to the experimental measurements. The measurements included retinal arteriolar and venular diameters and red blood cell (RBC) velocities, from which retinal blood flow was calculated. STZ induced decreases in vascular diameters and RBC velocities, resulting in an approximate 30% decrease in overall retinal blood flow. However, these decreases were not seen in mice given the three-week administration of vapiprost. Acute administration to diabetic mice of 1mg/kg vapiprost, but not 0.1mg/kg, induced arteriolar vasodilation, with the dilation more substantial in smaller feed arterioles. In summary, STZ-induced decreases in retinal blood flow can be attenuated by the thromboxane receptor antagonist vapiprost.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arterioles / drug effects
  • Arterioles / physiopathology
  • Biphenyl Compounds / pharmacology*
  • Blood Flow Velocity
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / physiopathology*
  • Drug Administration Schedule
  • Heptanoic Acids / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Thromboxane / antagonists & inhibitors*
  • Receptors, Thromboxane / metabolism
  • Receptors, Thromboxane / physiology
  • Retinal Artery / drug effects
  • Retinal Artery / physiopathology
  • Retinal Vein / drug effects
  • Retinal Vein / physiopathology
  • Retinal Vessels / drug effects*
  • Retinal Vessels / physiopathology
  • Vasoconstriction / drug effects*
  • Venules / drug effects
  • Venules / physiopathology

Substances

  • Biphenyl Compounds
  • Blood Glucose
  • Heptanoic Acids
  • Receptors, Thromboxane
  • vapiprost