Role of mineralocorticoid receptor on atrial structural remodeling and inducibility of atrial fibrillation in hypertensive rats.
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 DS+HS (186 ± 4 mm Hg) and DS+HS+EPL (184 ± 5 mm Hg) at 20 weeks. Burst atrial pacing demonstrated decreased AF inducibility in DS+HS+EPL (0 of 10) compared with DS+HS (7 of 10). Fibrosis and myocytes hypertrophy in the atrium were decreased in DS+HS+EPL 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.
Division of Cardiology, Niigata University School of Medical and Dental Sciences, Niigata City, Niigata, Japan.
Shinpei
S
Kimura
Masahiro
M
Ito
Makoto
M
Tomita
Makoto
M
Hoyano
Hiroaki
H
Obata
Limin
L
Ding
Masaomi
M
Chinushi
Haruo
H
Hanawa
Makoto
M
Kodama
Yoshifusa
Y
Aizawa
D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000503:physiopathology*; D006332:Cardiomegaly / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000077545:Eplerenone; D005355:Fibrosis; D006325:Heart Atria / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000502:physiology
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D000077545:Eplerenone; D020830:rac1 GTP-Binding Protein