Beneficial effects of a thromboxane receptor antagonist (BM 13.505) on platelet hyperreactivity and thromboxane formation in cholesterol-fed rabbits.
The effect of a thromboxane receptor antagonist (Daltroban, BM 13.505) on platelet function, vascular PGI2 formation and the severity of atherosclerotic lesions was studied in rabbits, fed for 4 months a cholesterol rich (1%) diet. Daltroban (10 mg/kg x day) significantly antagonized the hypercholesterolemia induced enhanced platelet aggregability, thromboxane formation and ATP secretion. The vascular PGI2 biosynthesis ("basal" or bradykinin stimulated), the number of PGI2 receptors on platelet membranes and the atherosclerotic plaque formation in the aorta were not affected by Daltroban. We suggest that in addition to a reduction of platelet hyperreactivity, protection of the vessel wall appears to be required for prevention of atherosclerosis in this model.
Löbel
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Institut für Pharmakologie, Universität Düsseldorf, F.R.G.
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D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D003094:Collagen; D004036:Diet, Atherogenic; D011464:Epoprostenol / Q000096:biosynthesis; D010648:Phenylacetates / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D002791:Cholesterol, Dietary; D010648:Phenylacetates; D013449:Sulfonamides; D013931:Thromboxanes; D000255:Adenosine Triphosphate; D003094:Collagen; D011464:Epoprostenol; C051762:daltroban