Sinzinger H, Lupattelli G, Kritz H, Fitscha P, O'Grady J
Wilhelm-Auerswald Atherosclerosis Research Group (ASF) Vienna, Austria.
Prostaglandins. 1996 Aug;52(2):77-91. doi: 10.1016/0090-6980(96)00054-8.
The in-vivo low-density lipoprotein (LDL)-uptake by the liver was monitored during the initial 60 minutes after injection of radiolabelled LDL. LDL-uptake by the liver as evidenced by the liver/blood pool ratio in normocholesterolemic male New Zealand white rabbits (44.2 +/- 3.1% of whole body activity) was almost double as compared to the ones fed a 1% cholesterol enriched diet (22.5 +/- 3.3%). The blood disappearance of 125I-LDL was significantly faster in normocholesterolemic animals. A 4-week treatment with the dihydropyridine calcium channel blocker isradipine resulted in a significantly enhanced LDL-binding by the liver, both in normo- and hypercholesterolemic animals to a comparable extent. A concomitant acetylsalicylic acid (ASA) treatment completely abolished the benefit induced by isradipine while ASA alone was ineffective. Similarly, 125I-LDL disappearance from blood was improved by isradipine, while ASA neutralizes this effect. Again, ASA alone did not change the kinetics. Plasma cholesterol and high-density lipoprotein (HDL) cholesterol remained unchanged. Isradipine significantly enhanced vascular prostaglandin(PG)I2-generation while concomitant ASA treatment or ASA application alone almost completely depressed PGI2-formation. It is concluded that the improved LDL-binding by the liver is due to an enhanced PGI2-formation evoked by isradipine.
在注射放射性标记的低密度脂蛋白（LDL）后的最初60分钟内，监测肝脏对LDL的体内摄取情况。正常胆固醇水平的雄性新西兰白兔肝脏对LDL的摄取（以肝脏/血池比率为指标，占全身活性的44.2±3.1%）与喂食富含1%胆固醇饮食的兔子相比（22.5±3.3%）几乎高出一倍。125I-LDL在正常胆固醇水平动物体内的血液清除速度明显更快。用二氢吡啶类钙通道阻滞剂伊拉地平进行为期4周的治疗，在正常胆固醇水平和高胆固醇水平的动物中，均可使肝脏对LDL的结合显著增强，且程度相当。同时给予乙酰水杨酸（ASA）治疗可完全消除伊拉地平带来的益处，而单独使用ASA则无效。同样，伊拉地平可改善血液中125I-LDL的清除，而ASA可抵消这种作用。单独使用ASA同样不会改变动力学。血浆胆固醇和高密度脂蛋白（HDL）胆固醇水平保持不变。伊拉地平可显著增强血管前列环素（PG）I2的生成，而同时给予ASA治疗或单独使用ASA几乎可完全抑制PGI2的形成。得出的结论是，肝脏对LDL结合的改善是由于伊拉地平引起的PGI2生成增强所致。
