Document Detail

Preventive effect of chronic endothelin type A receptor antagonist on coronary microvascular spasm induced by repeated epicardial coronary artery endothelial denudation in pigs.
MedLine Citation:
PMID:  20075598     Owner:  NLM     Status:  MEDLINE    
AIM: We investigated the role of endothelin-1 (ET-1) in coronary microvascular spasm in a porcine model. METHODS: A flowmeter was implanted around the left anterior descending coronary artery (LAD), and epicardial coronary artery endothelial denudation (ED) was performed just distal to the flowmeter every 2 weeks (W) until 6 W in 10 pigs (ED group). Ten pigs were chronically treated with endothelin type A receptor (ET(A)) antagonist (TA-0201, 0.1 mg/kg/day, ED+ET(A) group), while neither ED nor administration of ET(A) antagonist was performed in 12 pigs (Control group). We assessed changes in LAD blood flow and the denuded site diameter induced by acetylcholine (ACh, 0.05 microg/kg i.c.). RESULTS: In the ED group, administration of ACh to LAD induced zero flow without LAD diameter reduction at 8 W. In the ED+ET(A) group, the decrease in LAD blood flow response to ACh was suppressed. Chronic administration of TA-0201 suppressed ROS generation in the myocardium. Decreases of eNOS and intimal thickening were smaller in the TA-0201 administration group than the non-TA-0201 administration group. CONCLUSION: Chronic administration of ET(A) receptor antagonist is effective to prevent coronary microvascular spasm.
Taku Osugi; Shu-ichi Saitoh; Ken Matumoto; Mituru Muto; Kazuhiko Aikawa; Hiroshi Ohkawara; Kouichi Sugimoto; Masashi Kamioka; Toshiyuki Ishibashi; Yukio Maruyama
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Publication Detail:
Type:  Journal Article     Date:  2010-01-14
Journal Detail:
Title:  Journal of atherosclerosis and thrombosis     Volume:  17     ISSN:  1880-3873     ISO Abbreviation:  J. Atheroscler. Thromb.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-29     Completed Date:  2010-04-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9506298     Medline TA:  J Atheroscler Thromb     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  54-63     Citation Subset:  IM    
First Department of Internal Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.
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MeSH Terms
Acetylcholine / pharmacology
Body Weight
Coronary Circulation / drug effects,  physiology
Coronary Sinus / metabolism
Coronary Vasospasm / drug therapy*,  metabolism,  prevention & control*
Coronary Vessels / drug effects*,  metabolism
Disease Models, Animal
Endothelin-1 / metabolism
Endothelium, Vascular
Microcirculation / drug effects,  physiology
Nitric Oxide Synthase Type III / metabolism
Pyrimidines / pharmacology*
Reactive Oxygen Species / metabolism
Receptor, Endothelin A / antagonists & inhibitors*,  metabolism
Sulfonamides / pharmacology*
Sus scrofa
Vascular Resistance / drug effects,  physiology
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Endothelin-1; 0/Pyrimidines; 0/Reactive Oxygen Species; 0/Receptor, Endothelin A; 0/Sulfonamides; 0/T 0201; 0/Vasodilator Agents; 51-84-3/Acetylcholine; EC Oxide Synthase Type III

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

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