Effect of camonagrel, a selective thromboxane synthase inhibitor, on retinal vascularization in experimental diabetes.
Platelet hyperactivity accompanied by an increased synthesis of thromboxane and/or a decreased prostacyclin production are important factors in ischemic diabetic retinopathy. We studied the effect of camonagrel and dazoxiben, two thromboxane synthase inhibitors, on retinal vascularization in a model of streptozotocin-induced diabetes in rats. Ten nondiabetic rats, 10 diabetic animals treated with saline (i.e., not treated), and 60 diabetic animals treated with dazoxiben or camonagrel (10, 50 or 100 mg kg(-1) day(-1) p.o.) were studied. All treatments lasted for 90 days. Dazoxiben and camonagrel produced a dose-dependent reduction in platelet aggregation and thromboxane synthesis. Dazoxiben increased prostacylin synthesis by 78% at 100 mg kg(-1) day(-1), and camonagrel by 154%. Dazoxiben increased retinal vascularity by 74%, and by 183% after camonagrel treatment. Prostacyclin synthesis showed a direct linear correlation with the degree of retinal vascularization (r2=0.6733, P < 0.00001). We conclude that an increased prostacyclin synthesis may have a greater influence than the inhibition of thromboxane synthesis in preventing ischemic diabetic retinopathy in experimental diabetes. Camonagrel may be an alternative treatment in the prevention of these lesions.
De La Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
Moreno
A
A
Ruiz-Ruiz
M I
MI
García Campos
J
J
Sánchez de la Cuesta
F
F
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005342:Fibrinolysis / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015861:Retinal Neovascularization / Q000517:prevention & control*; D013311:Streptozocin; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007189:Indans; D010975:Platelet Aggregation Inhibitors; C029166:dazoxiben; D013929:Thromboxane B2; D013311:Streptozocin; D013930:Thromboxane-A Synthase; C103583:camonagrel