SULFONYLUREA AGENTS INHIBIT PLATELET-AGGREGATION AND [CA2-ACID(]I ELEVATION INDUCED BY ARACHIDONIC)

The effects of three hypoglycaemic agents-glimepiride, glibenclamide a nd 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 transm ission and by a newly-developed procedure using light scattering which allows the detection of small as well as large aggregates. Glimepirid e and glibenclamide inhibited the formation of small and large aggrega tes induced by optimal concentrations of arachidonic acid in a dose-de pendent manner. The ID50 values for the inhibition of platelet aggrega tion were approximately one third of those for arachidonic acid metabo lism, suggesting that both agents have certain direct inhibitory effec ts on platelet aggregation unrelated to arachidonic acid metabolism Gl iclazide inhibited the formation of small aggregates induced by low co ncentrations of arachidonic acid to a limited extent. However, it inhi bited the formation of large aggregates but not small aggregates when higher concentrations of arachidonic acid were used. Glimepiride and g libenclamide inhibited [Ca2+]i elevation induced by arachidonic acid i n a dose-dependent manner, whereas gliclazide had no inhibitory effect . Taken together, these suggest that gliclazide does not inhibit arach idonic acid metabolism but does have certain direct inhibitory effects on platelet aggregation.