Aspirin abolishes the decreased low-density lipoprotein (LDL) entry into the rabbit arterial wall induced by the calcium channel blocker isradipine.
After deendothelialization and experimentally induced hypercholesterolemia in rabbits, an increased LDL entry into the vascular wall can be monitored using radiolabelled LDL. In male rabbits aged 6 months the abdominal aortic endothelium was removed by a Fogarty catheter. The animals fed a 1% cholesterol supplemented diet were treated either with isradipine (0.3 mg/kg/daily) (n = 36) alone or in combination with aspirin (5 mg/kg/daily) (n = 36) for four weeks. Thirty-six animals served as controls. 1, 3, 6, 12, 24 and 48 hours prior to sacrificing, 10 microCi 125I-LDL was administered intravenously to six rabbits in each group. The LDL entry was quantified in the abdominal aorta according to morphologically assessed type of surface lining. Aortic cholesterol content was assessed by Sudan-III staining and quantitative determination. Endothelialized segments exhibited a significantly (p less than 0.05 - p less than 0.001) lower LDL uptake as compared to re- or deendothelialized segments. The LDL entry was significantly lower with isradipine treatment than in controls. In parallel the cholesterol content decreased and the Sudan-III-positive areas were smaller in size. This beneficial effect as well as that on aortic lipid content was abolished by a pretreatment with aspirin. While in the isradipine-treated animals PGI2 synthesis was significantly (p less than 0.01) enhanced, it was almost completely blocked by aspirin. These findings indicate that the benefit of reduced LDL entry caused by isradipine may be mediated by an increased endogenous PGI2 synthesis.
Sinzinger
H
H
Wilhelm Auerswald-Atherosclerosis Research Group (ASF) Vienna, Austria.
Virgolini
I
I
O'Grady
J
J
Keiler
A
A
Lupattelli
G
G
Angelberger
P
P
Molinari
E
E
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000037:antagonists & inhibitors*; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D017275:Isradipine / Q000037:antagonists & inhibitors*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D011817:Rabbits
D002121:Calcium Channel Blockers; D008077:Lipoproteins, LDL; D002784:Cholesterol; D011464:Epoprostenol; D001241:Aspirin; D017275:Isradipine