High glucose contributes to aspirin insensitivity in streptozotocin-diabetic rats: a multiparametric aggregation study.
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.
Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, University Hospital No. 2, Lodz, Poland. cwatala@csk.umed.lodz.pl
Cezary
C
Watala
Olga
O
Ulicna
Jacek
J
Golanski
Marek
M
Nocun
Iveta
I
Waczulíková
Leszek
L
Markuszewski
Józef
J
Drzewoski
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004351:Drug Resistance; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000139:chemically induced; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin