Sulphonylurea agents inhibit platelet aggregation and [Ca2+]i elevation induced by arachidonic acid

The effects of three hypoglycaemic agents--glimepiride, glibenclamide and gliclazide--were evaluated on platelet aggregation and intracellular Ca2+ elevation induced by arachidonic acid. Platelet aggregation was assessed both by the conventional method using changes in light transmission and by a newly-developed procedure using light scattering which allows the detection of small as well as large aggregates. Glimepiride and glibenclamide inhibited the formation of small and large aggregates induced by optimal concentrations of arachidonic acid in a dose-dependent manner. The ID50 values for the inhibition of platelet aggregation were approximately one third of those for arachidonic acid metabolism, suggesting that both agents have certain direct inhibitory effects on platelet aggregation unrelated to arachidonic acid metabolism. Gliclazide inhibited the formation of small aggregates induced by low concentrations of arachidonic acid to a limited extent. However, it inhibited the formation of large aggregates but not small aggregates when higher concentrations of arachidonic acid were used. Glimepiride and glibenclamide inhibited [Ca2+]i elevation induced by arachidonic acid in a dose-dependent manner, whereas gliclazide had no inhibitory effect. Taken together, these suggest that gliclazide does not inhibit arachidonic acid metabolism but does have certain direct inhibitory effects on platelet aggregation.