ORIGINAL ARTICLESHigh glucose contributes to aspirin insensitivity in streptozotocin-diabetic rats: a multiparametric aggregation studyWatala, Cezarya; Ulicna, Olgab; Golanski, Jaceka; Nocun, Mareka; Waczulíková, Ivetac; Markuszewski, Leszekd; Drzewoski, JózefeAuthor Information aDepartment of Haemostasis and Haemostatic Disorders, Medical University of Lodz, University Hospital No. 2, Lodz, Poland bPharmacobiochemical Laboratory, 3rd Department of Internal Medicine, Faculty of Medicine, Comenius University cDepartment of Nuclear Physics and Biophysics, Division of Biomedical Physics, Faculty of Mathematics, Physics, and Informatics, Comenius University, Bratislava, Slovakia dDepartment of Interventional Cardiology, Cardiodiabetology and Cardiac Rehabilitation, Medical University of Lodz, University Hospital No. 2 eDepartment of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland Received 25 July, 2005 Accepted 29 November, 2005 Correspondence and requests for reprints to Cezary Watala, Department of Haemostasis and Haemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Lodz, University Hospital No. 2, Zeromskiego 113, 90-549 Lodz, Poland Tel: +48 42 6393471; fax: +48 42 6787567; e-mail: [email protected], [email protected] Sponsorship: This study was supported from the project of the Polish State Committee for Scientific Research 3P05B10222, the funds from the Medical University of Lodz (502-11-698 and 503-130-2), the Slovak Grant Agency VEGA 1/3037/06 and 1/0546/03, as well as the NATO Cooperative Linkage Grant LST.CLG.980106. Blood Coagulation & Fibrinolysis: March 2006 - Volume 17 - Issue 2 - p 113-124 doi: 10.1097/01.mbc.0000203862.85610.ac Buy Metrics Abstract The effect of chronic hyperglycaemia on blood platelet response to acetylsalicylic acid was studied in rats with experimental diabetes. Platelet aggregation was determined in non-diabetic and streptozotocin-diabetic rats treated orally with 4 or 40 mg aspirin (ASA)/kg per day (for 8 weeks from the eighth day of diabetes) using whole blood impedance aggregometry with arachidonic acid or ADP as platelet agonists. The dose-dependent effect of ASA ‘therapy’ on ADP-agonized platelets was significant only in non-diabetic animals, while in diabetic rats both doses were ineffective in reducing ADP-stimulated platelet aggregation. ASA-mediated increased acetylation of platelet proteins favoured reduced platelet aggregation and slower platelet disaggregation (Pr < 0.025 or less). Interestingly, however, the occupation of platelet protein-free amino groups was significantly higher in control rats compared with diabetic rats (P < 0.001), pointing out that proteins of platelets in non-diabetic animals were more vulnerable for the ASA-induced acetylation. We conclude that chronic hyperglycaemia interferes with preventive effects of ASA on platelet reactivity. Our data validate the suggestion that the relationship between aspirin ineffectiveness and poor metabolic control, first revealed in humans, concerns also other animals' platelets and holds regardless of the model or type of diabetes. © 2006 Lippincott Williams & Wilkins, Inc.