Summary
This study determines the antiplatelet effects of oral ticlopidine (100 mg/kg × day)
in experimental hypercholesterolemia. Rabbits were fed either a standard diet or a
cholesterol-enriched diet (0.5% for 3 months, 1% for 1 month). In normocholesterolemic
controls ADP-, but not collagen-induced platelet aggregation was inhibited by ticlopidine
treatment. This was accompanied by a significantly enhanced inhibition of ADP-induced
platelet aggregation and stimulation of cyclic AMP accumulation by iloprost. Hypercholesterolemia
considerably attenuated the inhibition of ADP-induced aggregation by ticlopidine but
did not change its effect on the iloprost-induced inhibition of platelet function
and cyclic AMP formation. ADP-induced platelet-derived Llnumbuxane formation was considerably
greater in hypercholesterolemic rabbits and not reduced by ticlopidine. Ticlopidine
did also not significantly influence the extent and severity of atherosclerotic plaque
formation although a tendency for improvement was observed in a subgroup of animals.
The data suggest that hypercholesterolemia attenuates the inhibitory effect of ticlopidine
on A DP-induced platelet aggregation. This might be related to the stimulation of
thromboxane formation by ADP in hypercholesterolemia. The maintained protection from
ADP-induced inhibition of cAMP accumulation suggests a minor role of this mechanism
in the progression of hypercholesterolemia-induced vessel disease in this model.
