LAUSR

Aims: Ginsenoside Re (G‐Re), a major ginsenoside in ginseng, has many beneficial pharmacological effects on negative cardiac contractility, electromechanical alternans, antiarrhythmia, angiogenic regeneration and cardiac electrophysiological function. However, effects of G‐Re on gap‐junction remodeling are unclear. Therefore, this study aimed to investigate the effect of G‐Re on angiotensin II (Ang II)‐induced downregulation of connexin‐40 (CX40) and ‐43 (CX43) in beating rat left atria. Main methods: In this study, the isolated perfused beating rat atrial model was used and atrial gap‐junction remodeling was induced by Ang II. In vivo hemodynamic experiments were analyzed with a biological recorder. Changes in protein expression were analyzed by western blot. Key findings: G‐Re attenuated Ang II‐induced abnormal changes in heart rate, MAP, LVESP, LVEDP, +dp/dt max, −dp/dt min, P wave amplitude, P‐R interval and P wave length. This indicated a dose‐dependent preventive role against Ang II‐induced hyper hemodynamics in rats. Atrial activities of p38 mitogen‐activated protein kinase (MAPK), nuclear factor kappa‐B (NF‐&kgr;B) and activator protein 1 (AP‐1) were significantly increased by Ang II, as was expression of atrial collagen I and matrix metalloproteinase 2 (MMP2). Atrial CX40 and CX43 expression was downregulated by Ang II. These Ang II‐induced atrial effects were blocked by G‐Re, as well as rosiglitazone, an agonist of peroxisome proliferator‐activated receptor &ggr; (PPAR&ggr;), in a dose‐dependent manner. However, this inhibition was abolished by the PPAR&ggr; inhibitor GW9662. Significance: G‐Re may suppress Ang II‐induced downregulation of CX40 and CX43, by activating PPAR&ggr; signaling, in isolated perfused beating rat atria.