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

Abstract

Paper AbstractIntroduction. 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 (AT 1 -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. AT 1 -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.

Dynamics of Soluble Thrombomodulin and Circulating miRNAs in Patients with Atrial Fibrillation Undergoing Radiofrequency Catheter Ablation

“…The cut-off value of s-TM for AF recurrence was 10.07 U/mL, although specificity and sensitivity were relatively low. In an experimental rat model, rapid atrial pacing downregulated the gene expression of TM in atrial endocardium, 40 suggesting that the AF condition downregulated TM expression in the heart or endothelial cells and decreased serum s-TM.…”

Relationship Between Left Atrial Size and Stroke in Patients With Sinus Rhythm and Preserved Systolic Function

“…Alternatively, the LA enlargement may be a surrogate marker representing an adaptive response to some variously caused endothelial dysfunction that affects the systemic vascular bed. Endothelial dysfunction results from the abnormal regulation of and response to many different cytokines and paracrine hormones, including nitric oxide, angiotensin II and its receptor, plasminogen nhibitor I, thrombomodulin, and endothelin [ 19 ]. In particular, angiotensin II and its receptor are well-known 30 The Korean Journal of Internal Medicine Vol.…”

Coagulation Activity is Increased in the Left Atria of Patients With Paroxysmal Atrial Fibrillation During the Non-Paroxysmal Period Comparison With Chronic Atrial Fibrillation

“…25,26 This hypothesis is supported by a recently published report that indicated that angiotensin II receptor blockers could partially prevent atrial endothelial dysfunction and the occurrence of AF. 27,28 Apparently, intravascular thrombotic events in patients without AF are generally associated with abnormalities in vascular endothelial functioning and/or the coagulation system. In patients with pAF, endothelial dysfunction may also play an important role in thrombogenesis in the LA.…”