Concomitant aspirin treatment abolishes the antiatherosclerotic effects of the calcium channel blocker isradipine mediated by PGI2.
108 male rabbits, aged 6 months, with experimental hypercholesterolemia and experimental abdominal aortic lesioning received different regimen of antiatherosclerotic treatment; 36 of them were treated with isradipine, a dihydropyridine calcium antagonist (0.3 mg/kg/daily), 36 with isradipine in combination with aspirin whereas 36 animals received placebo. The entry of 125I-radiolabelled LDL into the aorta was demonstrated to be significantly diminished in isradipine-treated rabbits as well as positive Sudan-III-staining and aortic cholesterol content were in comparison to placebo. This benefit was almost completely abolished by concomitant aspirin-treatment. The notable increase in vascular prostacyclin (PGI2) is supposed to mediate the strong antiatherosclerotic effect of isradipine resulting in an inhibition of LDL-entry and vascular cholesterol accumulation. Aspirin almost totally blocked the raise in PGI2-synthesis by the inhibition of cyclooxygenase detected in isradipine-treated animals. It can be concluded, that aspirin-treatment may minimize the antiatherosclerotic actions of calcium antagonists which are mediated by the PG-system.
Pirich
C
C
Wilhelm-Auerswald Atherosclerosis Research Group (ASF) Vienna, Austria.
Lupattelli
G
G
Virgolini
I
I
Keiler
A
A
Gerakakis
A
A
Angelberger
P
P
Sinzinger
H
H
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D001161:Arteriosclerosis / Q000517:prevention & control*; D001241:Aspirin / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004095:Dihydropyridines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D017275:Isradipine; D007700:Kinetics; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D011817:Rabbits
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008077:Lipoproteins, LDL; D002784:Cholesterol; D011464:Epoprostenol; D001241:Aspirin; D017275:Isradipine