A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit.
This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (-9.0 to -5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (-6.0 log mol/L) was significantly (p less than 0.05) impaired in the experimental group (34.3 +/- 3.8%) compared with that in the control group (79.8 +/- 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 +/- 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 +/- 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.
Department of Medicine, University of Alberta, Edmonton, Canada.
C T
CT
Kappagoda
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AB
Thomson
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MP
Senaratne
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001391:Azo Compounds; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008855:Microscopy, Electron, Scanning; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D012977:Sodium Nitrite / Q000494:pharmacology; D013194:Staining and Labeling
D001391:Azo Compounds; D002791:Cholesterol, Dietary; D008055:Lipids; C033003:sudan red; D012977:Sodium Nitrite; D000109:Acetylcholine