Ginsenoside Re prevents angiotensin II-induced gap-junction remodeling by activation of PPARγ in isolated beating rat atria

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Abstract

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-κB) 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 γ (PPARγ), in a dose-dependent manner. However, this inhibition was abolished by the PPARγ inhibitor GW9662.

Significance:

G-Re may suppress Ang II-induced downregulation of CX40 and CX43, by activating PPARγ signaling, in isolated perfused beating rat atria.

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