Reduced platelet serotonin content in rabbits with dietary hypercholesterolemia

Serotonin [5-hydroxytryptamine (5-HT)] has been implicated in platelet acti vation and vasoconstriction, two processes that contribute to arterial thro mbosis in atherosclerotic diseases. In the present study, Japanese White ra bbits fed 1% cholesterol for 5 weeks were used to investigate the response of hypercholesterolemic vascular arteries and platelets to 5-HT. Contractio ns of the thoracic aorta induced by 5-HT were comparable between the choles terol-fed group and the age-matched control group. However, acetylcholine-i nduced vasodilation in arteries preconstricted with 5-HT was moderately but significantly attenuated in the cholesterol-fed rabbits. Platelet aggregat ion responses to 5-HT (0.1-3 mu mol/l) in combination with epinephrine (5 m u mol/l) adenosine diphosphate (ADP) (0.3-10 mu mol/l), 9,11-dideoxy-9 alph a,11 alpha-methanoepoxy-prostaglandin F-2 alpha (U-46619) (1-30 mu mol/l) o r collagen (3 mu g/ml) were significantly enhanced in cholesterol-fed rabbi ts. In contrast, platelet 5-HT content determined with a highperformance li quid chromatography-electrochemical detector (HPLC-ECD) was significantly d ecreased in cholesterol-fed rabbits. These results suggest a possible assoc iation among the endothelial dysfunction, platelet aggregation and platelet 5-HT content in rabbits with dietary hypercholesterolemia. Blood Coagul Fi brinolysis 11:313-319 (C) 2000 Lippincott Williams & Wilkins.