Prolongation of platelet survival in hypercholesterolaemic rabbits by CGS 12970 (3-methyl-2-(3-pyridyl)-1 indoleoctanoic acid) and dazoxiben.
In rabbits receiving a normal laboratory diet the platelet half-life was 40.4 +/- 2.5h (mean +/- S.D., n = 35). In animals fed the cholesterol-enriched diet for 12 weeks the platelet half-life was reduced to 31.6 +/- 3.6h (mean +/- S.D., n = 35). Treatment of cholesterol-fed animals with a single daily dose of CGS 12970 (a long acting inhibitor of thromboxane synthase) normalised the platelet half-life. Single daily doses of the relatively shorter acting thromboxane synthase inhibitors (CGS 13080 and dazoxiben) failed to correct the reduced platelet survival. However, twice daily dosing with dazoxiben was effective. The cyclooxygenase inhibitors, aspirin and sulphinpyrazone, failed to correct the reduced platelet survival.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D016861:Cyclooxygenase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood*; D007093:Imidazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D013442:Sulfinpyrazone / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D002791:Cholesterol, Dietary; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D011725:Pyridines; C029166:dazoxiben; D013929:Thromboxane B2; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D013930:Thromboxane-A Synthase; D001241:Aspirin; D013442:Sulfinpyrazone