Reduced platelet serotonin content in rabbits with dietary hypercholesterolemia.
Serotonin [5-hydroxytryptamine (5-HT)] has been implicated in platelet activation and vasoconstriction, two processes that contribute to arterial thrombosis in atherosclerotic diseases. In the present study, Japanese White rabbits fed 1% cholesterol for 5 weeks were used to investigate the response of hypercholesterolemic vascular arteries and platelets to 5-HT. Contractions of the thoracic aorta induced by 5-HT were comparable between the cholesterol-fed group and the age-matched control group. However, acetylcholine-induced vasodilation in arteries preconstricted with 5-HT was moderately but significantly attenuated in the cholesterol-fed rabbits. Platelet aggregation responses to 5-HT (0.1-3 micromol/l) in combination with epinephrine (5 micromol/l), adenosine diphosphate (ADP) (0.3-10 micromol/l), 9,11-dideoxy-9alpha,11alpha-methanoepoxy-prostaglandin F2alpha (U-46619) (1-30 micromol/l) or collagen (3 microg/ml) were significantly enhanced in cholesterol-fed rabbits. In contrast, platelet 5-HT content determined with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) was significantly decreased in cholesterol-fed rabbits. These results suggest a possible association among the endothelial dysfunction, platelet aggregation and platelet 5-HT content in rabbits with dietary hypercholesterolemia.
Ogawa
T
T
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan. togawa@shina.sankyo.co.jp
Sugidachi
A
A
Asai
F
F
Koike
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood* / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012701:Serotonin / Q000097:blood* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002791:Cholesterol, Dietary; D016166:Free Radical Scavengers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D012701:Serotonin; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine