title: Prostaglandin I2-mediated upregulation of 125I-LDL-receptor binding by isradipine in normo- and hypercholesterolemic rabbits in vivo.
abstract: 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.
authors.affiliation: Wilhelm-Auerswald Atherosclerosis Research Group (ASF) Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Sinzinger
authors.forename: G
authors.initials: G
authors.lastname: Lupattelli
authors.forename: H
authors.initials: H
authors.lastname: Kritz
authors.forename: P
authors.initials: P
authors.lastname: Fitscha
authors.forename: J
authors.initials: J
authors.lastname: O'Grady
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015331:Cohort Studies; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000378:metabolism*; D007457:Iodine Radioisotopes; D017275:Isradipine / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D007457:Iodine Radioisotopes; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D011464:Epoprostenol; D017275:Isradipine