Document Detail


Valsartan alleviates atherosclerotic lesions in pulmonary arteries of rabbits via an endothelium-dependent mechanism.
MedLine Citation:
PMID:  20306886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Angiotensin II plays an important role in the pathogenesis of atherosclerosis. This study was designed to examine the effect of valsartan, an angiotensin receptor blocker, on atherosclerotic lesions in pulmonary arteries of rabbits with atherosclerosis induced by a high-cholesterol (HC) diet. METHODS: Male New Zealand rabbits were randomly divided into four groups: control, HC without valsartan, HC with 3 mg/kg/d valsartan, and HC with 10 mg/kg/d valsartan. Following 12 weeks of treatment, serum lipid profiles were determined. Pulmonary arteries were harvested and stained with Sudan IV for evaluation of atherosclerotic lesions. The middle lobes of the rabbit lungs were isolated, embedded in paraffin, and sectioned and stained with haematoxylin and eosin. Nitric oxide (NO) and endothelin-1 (ET-1) levels were determined in pulmonary arteries by nitrate reductase assay and radioimmunoassay, respectively. RESULTS: HC feeding altered serum lipid levels and induced atherosclerotic lesions in pulmonary arteries. Although 12 weeks of valsartan treatment failed to alter serum lipid levels, it significantly ameliorated HC-induced atherosclerotic lesions. Lesion areas, inflammatory cell infiltration, and occlusions of small arteries of lungs were reduced. Moreover, the endothelium-derived NO levels in pulmonary arteries were increased by valsartan treatment (10 mg/kg/d) compared to levels in the HC group. ET-1 levels were decreased by valsartan treatment compared to levels in the HC group. NO and ET-1 levels were not altered by valsartan at 3 mg/kg/d. CONCLUSION: Our data demonstrates that HC diet-induced atherosclerotic lesions in rabbit pulmonary arteries can be ameliorated by treatment with valsartan, possibly through a NO and ET-1-dependent mechanism.
Authors:
Yuanshi Li; Lu Fu; Qianping Gao; Dan Ma
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Acta cardiologica     Volume:  65     ISSN:  0001-5385     ISO Abbreviation:  Acta Cardiol     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-03-23     Completed Date:  2010-04-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370570     Medline TA:  Acta Cardiol     Country:  Belgium    
Other Details:
Languages:  eng     Pagination:  23-9     Citation Subset:  IM    
Affiliation:
The first affiliated hospital of Harbin Medical University, Harbin, China.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II Type 1 Receptor Blockers / administration & dosage,  therapeutic use*
Animals
Atherosclerosis / drug therapy*,  physiopathology
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelin-1 / metabolism
Endothelium, Vascular / drug effects,  physiopathology*
Lipids / blood
Male
Nitric Oxide / metabolism
Pulmonary Artery* / metabolism,  pathology,  physiopathology
Rabbits
Tetrazoles / administration & dosage,  therapeutic use*
Treatment Outcome
Valine / administration & dosage,  analogs & derivatives*,  therapeutic use
Vasodilation / drug effects*
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Endothelin-1; 0/Lipids; 0/Tetrazoles; 10102-43-9/Nitric Oxide; 137862-53-4/valsartan; 7004-03-7/Valine

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