Effects of chronic administration of ethanol on platelets from rabbits with diet-induced hypercholesterolemia. Unchanged characteristics and responses to ADP but reduction of enhanced thrombin-induced, TxA2-independent platelet responses.
To investigate the effect on platelet function of the interaction between dietary cholesterol and moderate, chronic doses of ethanol, hypercholesterolemia was induced in rabbits by 8 weeks of administration of a chow diet with added (0.25% wt/wt) cholesterol; during the eighth week, a moderate amount of ethanol (6% in drinking water) was given. Blood alcohol levels were not detectable in ethanol-treated rabbits at the time of exsanguination. Ethanol did not affect plasma cholesterol levels or the cholesterol to phospholipid molar ratio in platelets. Platelet membrane fluidity, which decreased with cholesterol feeding, was not altered further by administration of ethanol. The overall fatty acid composition of platelet phospholipids was not affected by either cholesterol feeding or chronic ethanol intake. Responses of washed platelets stimulated with either ADP or thrombin were studied to determine whether ethanol administration modified platelet functions in hypercholesterolemia. Primary ADP-induced aggregation was not affected by cholesterol feeding or chronic ethanol intake, but thrombin-induced aggregation and secretion of [14C]serotonin from prelabeled platelets, which were enhanced by cholesterol feeding, were diminished by administration of ethanol to hypercholesterolemic rabbits. This reduction in thrombin-induced responses was also observed with aspirin-treated platelets, which cannot form thromboxane A2. Thus, chronic short-term administration of a moderate amount of ethanol inhibited the enhanced responses of platelets from rabbits with diet-induced hypercholesterolemia, via a thrombin-induced, thromboxane A2-independent pathway.
Latta
E K
EK
Department of Biochemistry, University of Toronto, Ontario, Canada.
Packham
M A
MA
DaCosta
S M
SM
Rand
M L
ML
D000244:Adenosine Diphosphate / Q000502:physiology; D000437:Alcoholism / Q000503:physiopathology*; D000821:Animal Feed; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002250:Carbon Radioisotopes; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000209:etiology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors
D002250:Carbon Radioisotopes; D002791:Cholesterol, Dietary; D012701:Serotonin; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D013917:Thrombin