Role of mineralocorticoid receptor on atrial structural remodeling and inducibility of atrial fibrillation in hypertensive rats

Abstract

Hypertension is well known to increase atrial fibrillation (AF) and the development of AF is associated with atrial chamber remodeling. Although mineralocorticoid receptor (MR) inhibition provides cardiovascular protection, the role of MR on atrial structural remodeling and inducibility of AF in hypertension remains unclear. Here, we investigated roles of the MR on atrial structural remodeling and inducibility of AF in hypertensive rats by using MR antagonist eplerenone (EPL). Dahl salt-sensitive (DS) rats were fed a normal-salt or a high-salt (HS) diet from 7 weeks, and a non-antihypertensive dose of EPL or vehicle was administrated from 13 weeks, at which time myocytes hypertrophy, interstitial fibrosis in the atrium and AF inducibility had increased, until 20 weeks. There was no significant difference in systolic blood pressure between DSHS (1864 mm Hg) and DSHSEPL (1845 mm Hg) at 20 weeks. Burst atrial pacing demonstrated decreased AF inducibility in DSHSEPL (0 of 10) compared with DSHS (7 of 10). Fibrosis and myocytes hypertrophy in the atrium were decreased in DSHSEPL with the reduction of atrial inflammatory cytokines. These beneficial effects of EPL were associated with less atrial oxidative stress, as assessed by 4-hydroxy-2-nonenal staining, and reduced activation of the Rho GTPase Rac1 in the atrium. Thus, MR has important roles in atrial structural remodeling and AF inducibility in Dahl rats. The effects of MR are associated, at least in part, with activation of Rac1-oxidative stress/inflammatory axis. © 2011 The Japanese Society of Hypertension All rights reserved.