Effects of daltroban, a thromboxane (TX) A2 receptor antagonist, on lipid metabolism and atherosclerosis.
In rat hepatocyte cultures daltroban reduced 14C-acetate incorporation stronger into cholesterol (CH) esters than into free CH. Further data suggest that the reduction of cellular sterols by daltroban is independent from its TXA2 receptor antagonistic activity and caused by reduced capacity of ACAT depending CH esterification. In rabbits fed CH-enriched diet treatment with daltroban led to an inhibition of platelet aggregation and to a significant reduction of progression of atherosclerosis. Both reduced CH esterification and TXA2 receptor antagonism may contribute to the diminution of progression of atherosclerosis by daltroban.
Pill
J
J
Preclinical Research Department, Boehringer Mannheim GmbH, FRG.
Metz
J
J
Stegmeier
K
K
Hartig
F
F
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000096:biosynthesis; D003324:Coronary Artery Disease / Q000097:blood / Q000517:prevention & control*; D004036:Diet, Atherogenic; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D010648:Phenylacetates / Q000494:pharmacology* / Q000627:therapeutic use; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002788:Cholesterol Esters; D010648:Phenylacetates; D011450:Prostaglandin Endoperoxides, Synthetic; D013449:Sulfonamides; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002785:Sterol O-Acyltransferase; C051762:daltroban