Volume 8, Number 3, September 2007

Angiotensin type 1 receptor blockade prevents endocardial dysfunction of rapidly paced atria in rats
Takeshi Yamashita, Akiko Sekiguchi, Takeshi Kato, Takayuki Tsuneda, Yu-ki Iwasaki, Kouichi Sagara, Hiroyuki Iinuma, Hitoshi Sawada, Tadanori Aizawa

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.

JRAAS 2007;8:127-132.

View full PDF article (open in new window)
Export to bibliographic software or plain text
Email this article

Right click on this DOI link and copy link to cite this article (What is a DOI link?)