title: Antiatherosclerotic effects of oral cicaprost in experimental hypercholesterolemia in rabbits.
abstract: The efficacy of the oral prostacyclin mimetic cicaprost in preventing atheromatous plaque formation was studied in an in vivo model of experimental hypercholesterolemia. New Zealand white rabbits were fed either standard chow or a cholesterol-enriched (1%) diet for 12 weeks. Cicaprost was added to the drinking water in a non-hypotensive dose (5 micrograms/kg/day) and withdrawn 3 days prior to studying platelet, leukocyte and endothelial function. In cholesterol-fed rabbits, oral cicaprost reduced the aortic intimal surface covered by atheromatous lesions from 84 to 63% (P < 0.05). There was no major difference in serum lipid composition between cicaprost- and vehicle-treated animals. In hyper-cholesterolemic rabbits there was a significant impairment of endothelium-dependent relaxations. Cicaprost treatment considerably improved this endothelial function but had no effect in rabbits receiving standard diet. In addition, platelet and leukocyte hyperreactivity, as seen in hypercholesterolemic rabbits, were largely reduced by cicaprost treatment. These data are the first to demonstrate marked antiatherosclerotic effects of long-term oral prostacyclin treatment. The mechanism may be related to improved endothelial function and subsequent prevention of secondary platelet and neutrophil hyperreactivity.
authors.affiliation: Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Braun
authors.forename: T
authors.initials: T
authors.lastname: Hohlfeld
authors.forename: P
authors.initials: P
authors.lastname: Kienbaum
authors.forename: A A
authors.initials: AA
authors.lastname: Weber
authors.forename: M
authors.initials: M
authors.lastname: Sarbia
authors.forename: K
authors.initials: K
authors.lastname: Schrör
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use; D011817:Rabbits
chemical_list: D011465:Prostaglandins, Synthetic; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D000109:Acetylcholine; C043867:cicaprost