Effect of aspirin plus dipyridamole on the retinal vascular pattern in experimental diabetes mellitus.
Platelet hyperactivity has been one of the mechanisms implicated in the pathogenesis of diabetic retinopathy. Antiplatelet agents have been shown, in experimental models, to prevent the development of retinal vascular abnormalities when given from the first day after the onset of diabetes. We assessed the effect of aspirin plus dipyridamole (6 + 12 mg/kg daily) on the retinal vascular pattern in experimental streptozotocin-induced diabetes in rats, when the treatment was given at different intervals after the induction of diabetes, over a 3-month study period. Saline-pretreated diabetic rats showed a time-dependent increases in the platelet production of thromboxane B2 (r = 0.981, P < .0001) and a decrease in the aortic production of 6-keto-PGF1 alpha. The percentage of retinal area occupied by horseradish peroxidase-labeled vessels decreased progressively in relation to the length of time of the evolution of diabetes (r = 0.983, P < .00001) and the thromboxane/prostacyclin ratio. Treatment with aspirin plus dipyridamole caused an inhibition of the platelet production of thromboxane B2 and a decrease in the vascular synthesis of prostacyclin. Treatment with antiplatelet agents slowed down the decrease in the percentage of retinal area occupied by horseradish peroxidase-labeled vessels. These data provide further evidence to support the results of previous clinical trials in which antiplatelet agents had a beneficial effect on the evolution of retinal lesions in early diabetic retinopathy.
De la Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
Moreno
A
A
Muñoz
M
M
García Campos
J M
JM
Sánchez de la Cuesta
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D004176:Dipyridamole / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D013311:Streptozocin
D010975:Platelet Aggregation Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D013311:Streptozocin; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin