Effect of aspirin on prostanoids and nitric oxide production in streptozotocin-diabetic rats with ischemic retinopathy.
The importance in experimental diabetic retinopathy of prostacyclin and nitric oxide (NO), as well as the possible effect of acetylsalicylic acid (ASA), are well known. To investigate the effect of two doses of aspirin in the prevention of retinal ischemia in streptozotocin-diabetic rats, we compared nondiabetic rats and diabetic rats after 1, 2 and 3 months of diabetes, and diabetic rats treated with 2 mg or 10 mg ASA/kg per day p.o. from the first day of diabetes. The parameters determined after 1, 2 and 3 months of development were platelet aggregation, thromboxane B(2) (TxB(2)) production, 6-keto-prostaglandin F(1)(alpha) (stable metabolite of prostacyclin), NO, plasma nitrites/nitrates, and percentage retinal surface occupied by horseradish peroxidase (HRP)-permeable vessels. In diabetic rats platelet aggregation and thromboxane concentration were increased, and prostacyclin, NO and area occupied by HRP-permeable vessels were decreased. Acetylsalicylic acid reduced platelet aggregation, and lowered thromboxane production by 82%-99%. Prostacyclin production was inhibited by 92%-95% with 10 mg ASA/kg per day, and by 8%-20% with 2 mg ASA/kg per day. In diabetic rats NO production increased after 2 and 3 months of treatment to levels seen in nondiabetic rats. The reduction in HRP-permeable retinal surface decreased from a maximum of 87% in DR to 51% after treatment with 2 mg ASA/kg per day, and to 62% after 10 mg ASA/kg per day. We conclude that ASA (2 mg/kg per day and 10 mg/kg per day) increased NO production in streptozotocin-diabetic rats and reduced the degree of retinal ischemia.
De La Cruz
P
P
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain. jpcruz@uma.es
Guerrero
A
A
Paniego
J
J
Arranz
I
I
Moreno
A
A
Sánchez De La Cuesta
F
F
D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000150:complications; D003930:Diabetic Retinopathy / Q000097:blood* / Q000209:etiology / Q000517:prevention & control; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism*
D009566:Nitrates; D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D001241:Aspirin