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Angiotensin type 1 receptor blockade prevents endocardial dysfunction of rapidly paced atria in rats

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Akiko Sekiguchi

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Takeshi Kato

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Takayuki Tsuneda

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Yu-ki Iwasaki

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Kouichi Sagara

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Hiroyuki Iinuma

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Hitoshi Sawada

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Tadanori Aizawa

The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan

Introduction. Atrial fibrillation (AF) per se causes atrial endocardial dysfunction leading to local coagulation imbalance on the internal surface of the atrium, which contributes to thrombus formation in the fibrillating left atrium.

Materials and methods. To test a hypothesis that blockade of angiotensin II type 1 receptor (AT1-receptor) prevents the endocardial dysfunction by AF, we examined the effects of olmesartan on the expression of tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) in the endocardium of the rapidly paced rat atria.

Results. Rapid pacing induced a significant decrease in TFPI,TM and eNOS and an increase in PAI-1 protein in the left atrium. Pre-administration of low-dose olmesartan significantly prevented the down-regulation of TFPI,TM and eNOS and also attenuated the up-regulation of PAI-1. Immunohistochemistry identified these changes predominantly in the atrial endocardium. While the drug was without any effect on mRNA levels of TFPI,TM and eNOS, there was a significant decrease in its PAI-1 mRNA expression.

Conclusions. AT1-receptor blocker could partially prevent the atrial endocardial dysfunction by rapid atrial pacing, which would provide one theoretical basis for beneficial effects for stroke prevention in AF.

Key Words: angiotensin II • anticoagulants • endocardium • fibrillation • olmesartan

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 8, No. 3, 127-132 (2007)
DOI: 10.3317/jraas.2007.021


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Yamashita, T. Articles by Aizawa, T. Search for Related Content PubMed PubMed Citation Articles by Yamashita, T. Articles by Aizawa, T. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Atrial Fibrillation Heart Diseases Social Bookmarking                         What's this?