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Research Article| Volume 103, ISSUE 1, P93-105, October 1993

Antiatherosclerotic effects of oral cicaprost in experimental hypercholesterolemia in rabbits

DOI:https://doi.org/10.1016/0021-9150(93)90043-T
Antiatherosclerotic effects of oral cicaprost in experimental hypercholesterolemia in rabbits
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      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 Cicaprost was added to the drinking water in a non-hypotensive dose (5 μg/kg/day) and withdrawn 3 days prior to studying platelet, leukocyte and endothelial function.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 hypercholesterolemic 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.

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      Article info

      Publication history

      Accepted: June 8, 1993
      Received in revised form: April 21, 1993
      Received: December 17, 1992

      Identification

      DOI: https://doi.org/10.1016/0021-9150(93)90043-T

      Copyright

      © 1993 Elsevier Scientific Publishers Ireland Ltd. All rights reserved. Published by Elsevier Inc.

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