title: Nitric oxide-cGMP and prostacyclin-cAMP pathways in patients with type II diabetes and different types of retinopathy.
abstract: The aim of this study was to investigate two factors of endothelial dysfunction and their platelet second messengers in patients with type II diabetes and different types of retinopathy. We compared 20 healthy volunteers and 117 patients with type II diabetes (34 with no signs of diabetic retinopathy, 26 with background diabetic retinopathy, 29 with ischemic-proliferative diabetic retinopathy and 28 with edematous diabetic retinopathy). The following parameters were recorded: platelet aggregometry, nitrites, 6-keto-prostaglandin-F(1alpha) and intraplatelet cAMP and cGMP. Platelet aggregation was greater in patients with diabetic retinopathy. The concentration of ADP that produced 50% maximum intensity of aggregation was 1.81 microM in patients without diabetic retinopathy, 0.92 microM in patients with background diabetic retinopathy, 0.85 microM in patients with ischemic-proliferative diabetic retinopathy and 0.44 microM in patients with edematous diabetic retinopathy. The platelets in these patients were more resistant to inhibition by SIN-1 (concentrations of SIN-1 that produced 50% inhibition of maximum intensity of collagen-induced aggregation in the four patient groups: 18.1, 13.6, 16.2 and 33.2 microM, respectively). Nitrite concentration in patients with ischemic-proliferative diabetic retinopathy was one sixth of the value in healthy controls, but there was no significant difference between the control group and patients with edematous diabetic retinopathy. In the latter group, neutrophils increased nitrite production by 68.7 +/- 3%, whereas in patients with ischemic-proliferative diabetic retinopathy, this increase was 18.7 +/- 2.0%. We conclude that nitric oxide production is higher in patients with type II diabetes and edematous retinopathy than in those with ischemic-proliferative retinopathy. This finding, together with the possibly greater production of free radicals, may explain the greater impairment of platelet function in the former patients.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Málaga, Spain. jpcruz@uma.es
authors.forename: J P
authors.initials: JP
authors.lastname: De La Cruz
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.forename: G
authors.initials: G
authors.lastname: Ortega
authors.forename: J A
authors.initials: JA
authors.lastname: González-Correa
authors.forename: F
authors.initials: F
authors.lastname: Sánchez de la Cuesta
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000368:Aged; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism*; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
chemical_list: D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP