Division of Cardiology, Niigata University School of Medical and Dental Sciences, Niigata City, Niigata, Japan.
Hypertens Res. 2011 May;34(5):584-91. doi: 10.1038/hr.2010.277. Epub 2011 Jan 20.
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.
高血压众所周知会增加心房颤动（AF）的发生，而 AF 的发生与心房腔重构有关。尽管盐皮质激素受体（MR）抑制可提供心血管保护，但 MR 在高血压中心房结构重构和 AF 易感性中的作用仍不清楚。在这里，我们通过使用 MR 拮抗剂依普利酮（EPL）研究了 MR 在高血压大鼠心房结构重构和 AF 易感性中的作用。Dahl 盐敏感（DS）大鼠从 7 周开始给予正常盐或高盐（HS）饮食，从 13 周开始给予非抗高血压剂量的 EPL 或载体，此时心肌肥大、心房间质纤维化和 AF 易感性增加，直到 20 周。20 周时，DS+HS（186±4mmHg）和 DS+HS+EPL（184±5mmHg）之间的收缩压没有显著差异。心房起搏显示 DS+HS+EPL 组（0/10）的 AF 易感性较 DS+HS 组（7/10）降低。DS+HS+EPL 组心房纤维化和心肌肥大减少，同时心房炎症细胞因子减少。EPL 的这些有益作用与心房氧化应激减少有关，如 4-羟基-2-壬烯醛染色所示，以及心房 Rac1 的 Rho GTPase 活性降低有关。因此，MR 在 Dahl 大鼠的心房结构重构和 AF 易感性中具有重要作用。MR 的作用至少部分与 Rac1-氧化应激/炎症轴的激活有关。
