Effect of DT-TX 30, a combined thromboxane synthase inhibitor and thromboxane receptor antagonist, on retinal vascularity in experimental diabetes mellitus.
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.
De La Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain. jpcruz@uma.es
Moreno
A
A
Ruiz-Ruiz
M I
MI
Sánchez De La Cuesta
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002722:Chlorobenzenes / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects* / Q000254:growth & development*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D001786:Blood Glucose; D002722:Chlorobenzenes; C107837:DTTX30; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D017482:Receptors, Thromboxane; C029166:dazoxiben; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003094:Collagen; D013930:Thromboxane-A Synthase