The pyrimido-pyrimidine derivatives, dipyridamole, mopidamol and RA-642, prevent from retinal vascular defects in experimental diabetes mellitus.
We compared the effects of dipyridamole, RA-642, and mopidamol on platelet activity and thromboxane/prostacyclin balance in relation to the degree of retinal vascularization in a model of experimental streptozotocin-induced diabetes in rats. After 3 months, collagen-induced platelet aggregation in whole blood was 25% higher in diabetic animals than in nondiabetics. Dipyridamole inhibited 43% platelet aggregation, mopidamol 39%, and RA-642 36%. Platelet production of thromboxane B2 was 87% higher in untreated diabetic rats. Mopidamol and RA-642 produced a 46% and 41% inhibition of thromboxane B2. Dipyridamole did not inhibited thromboxane B2 synthesis. Aortic production of 6-keto-PGF1 alpha was 43% lower in untreated diabetic animals and showed no change after treatment with either mopidamol or RA-642. In contrast, dipyridamole caused a 90% increase in aortic production of prostacyclin. Computerized analysis of retinal vascularization showed that untreated diabetic rats had a 81% decrease in the area occupied by peroxidase-labelled vessels as compared with nondiabetics. Treatment with dipyridamole, mopidamol, and RA-642 caused 2.5-fold, 2.8-fold and four-fold increases, respectively, in the percentage of retinal surface occupied by peroxidase-labelled vessels. Differences in retinal vascularization between diabetic animals given RA-642 and nondiabetic controls were negligible.
De La Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Malaga, Spain.
Moreno
A
A
Mérida
F
F
García Campos
J
J
Sánchez de la Cuesta
F
F
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000517:prevention & control*; D004176:Dipyridamole / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D008297:Male; D009012:Mopidamol / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000378:metabolism
D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; D011743:Pyrimidines; D013931:Thromboxanes; D009012:Mopidamol; C010650:RA 642; D004176:Dipyridamole; D011464:Epoprostenol