Effect of DT-TX 30, a Combined Thromboxane Synthase Inhibitor and Thromboxane Receptor Antagonist, on Retinal Vascularity in Experimental Diabetes Mellitus

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 B 2 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 r 2=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.