Document Detail


Long-term probucol treatment reverses the severity of myocardial injury in watanabe heritable hyperlipidemic rabbits.
MedLine Citation:
PMID:  9409258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that administration of NO donors ameliorates the severity of myocardial injury in cholesterol-fed rabbits. We now evaluated the effects of probucol, a lipid-lowering antioxidant that can preserve endothelium-dependent relaxation (EDR), in the aortas of cholesterol-fed rabbits. We examined the effects of short-term (7 days) or long-term (24 weeks) administration of 1% probucol on the size of infarcts resulting from 30 minutes of coronary occlusion followed by reperfusion (for 48 hours) in Watanabe heritable hyperlipidemic (WHHL) rabbits. Infarcts in untreated WHHL rabbits were significantly larger than those in the rabbits receiving the long-term but not the short-term treatment with probucol (72.2 +/- 5.4%, 37.6 +/- 6.4%, and 66.7 +/- 3.5%, respectively). Long-term probucol treatment also significantly reduced myeloperoxidase activity in both ischemic and nonischemic myocardium and suppressed P-selectin expression in the coronary vasculature. No significant differences were observed in hemodynamic parameters during myocardial ischemia/reperfusion. Long-term probucol treatment significantly reduced the surface area of atherosclerotic plaque lesions in the aorta (24.4 +/- 3.8% vs 46.3 +/- 6.3, P < .05). Moreover, long-term probucol treatment restored acetylcholine-induced EDR in aortic rings but did not affect sodium nitroprusside-induced relaxation. Finally, long-term probucol treatment resulted in significantly elevated cGMP levels in the aorta. These results indicate that long-term probucol treatment significantly ameliorates myocardial injury in heritable atherosclerotic rabbits, perhaps by reducing the accumulation of leukocytes in the myocardium and atherosclerotic vascular lesions. Thus, long-term administration appears to suppress the progression of atherosclerotic vascular disease in this animal model.
Authors:
S Hoshida; N Yamashita; J Igarashi; K Aoki; T Kuzuya; M Hori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  17     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-01-22     Completed Date:  1998-01-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2801-7     Citation Subset:  IM    
Affiliation:
First Department of Medicine, Osaka University Medical School, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Antilipemic Agents / administration & dosage,  pharmacology,  therapeutic use*
Antioxidants / administration & dosage,  pharmacology,  therapeutic use*
Aorta, Thoracic / pathology
Aortic Diseases / etiology,  pathology
Arteriosclerosis / etiology,  pathology
Coronary Disease / blood,  etiology
Coronary Vessels / drug effects,  metabolism
Disease Progression
Drug Administration Schedule
Hyperlipidemias / blood,  complications*,  genetics
Male
Myocardial Infarction / drug therapy*,  etiology,  pathology
Myocardium / enzymology
P-Selectin / biosynthesis
Peroxidase / analysis
Probucol / administration & dosage,  pharmacology,  therapeutic use*
Rabbits
Chemical
Reg. No./Substance:
0/Antilipemic Agents; 0/Antioxidants; 0/P-Selectin; 23288-49-5/Probucol; EC 1.11.1.7/Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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