Effect of DT-TX 30, a combined thromboxane synthase inhibitor and thromboxane receptor antagonist, on retinal vascularity in experimental diabetes mellitus

Thromb Res. 2000 Feb 1;97(3):125-31. doi: 10.1016/s0049-3848(99)00173-5.

Abstract

Combined thromboxane synthase inhibitors and thromboxane receptors antagonists have been shown to have a beneficial effect on different models of thrombosis in vivo. We studied the action of one of these compounds (DT-TX 30) compared with dazoxiben (a thromboxane synthase inhibitor) on retinal vascularity in streptozotocin-diabetic rats. Ten nondiabetic animals were treated with isotonic saline, 30 (10 animals per group) were given 0.4, 4, and 8 mg kg(-1) per day of DT-TX 30 (p.o.) and 30 (10 animals per group) were given 10, 50, and 100 mg kg(-1) per day of dazoxiben (p.o.) over a 90-day study period. DT-TX 30 caused a dose-dependent decrease of platelet aggregation and thromboxane B2 synthesis. There was an increase of 9, 65, and 166% in the synthesis of prostacyclin after treatment with 0.4, 4, and 8 mg kg(-1) per day, respectively. Retinal vascularity increased in 51, 72, and 182% of animals in response to the three doses used. Synthesis of prostacyclin and the degree of retinal vascularity showed a linear correlation (r2=0.6528,p<0.00001). Dazoxiben, at doses that inhibited thromboxane synthesis as much as DT-TX 30, increased prostacyclin production and retinal vascularity with less potency than DT-TX 30. In conclusion, the antagonism of thromboxane receptors may be an important additional effect to the inhibition of thromboxane synthase in the prevention of ischemic retinal lesions in experimental diabetes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / blood
  • Animals
  • Blood Glucose / drug effects
  • Chlorobenzenes / pharmacology*
  • Collagen / pharmacology
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / prevention & control
  • Enzyme Inhibitors / pharmacology
  • Imidazoles / pharmacology
  • Male
  • Platelet Aggregation / drug effects
  • Pyridines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Thromboxane / antagonists & inhibitors*
  • Receptors, Thromboxane / metabolism
  • Retinal Vessels / drug effects*
  • Retinal Vessels / growth & development*
  • Thromboxane B2 / blood
  • Thromboxane-A Synthase / antagonists & inhibitors*
  • Thromboxane-A Synthase / pharmacology

Substances

  • Blood Glucose
  • Chlorobenzenes
  • DTTX30
  • Enzyme Inhibitors
  • Imidazoles
  • Pyridines
  • Receptors, Thromboxane
  • dazoxiben
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • Collagen
  • Thromboxane-A Synthase