| Background:Atrial fibrillation (AF) remains one of the most common sustained arrhythmia in clinical practice. The number of people affected by AF has been increasing. It is projected that the prevalence of AF will rise from 5.2 million in 2010 to 12.1 million in 2030 in the USA. AF results from a complex interaction of several predisposing factors, such as aging, valvular heart disease, coronary artery disease, thyroid disease, chronic obstructive pulmonary disease, diabetes mellitus, etc; but the most prevalent risk factor is hypertension. The role of hypertension in the development of AF was also well established by epidemiology study.It has been nearly 20 years since Haissaguerre demonstrated that the pulmonary veins (PVs) played a critical role in the mechanism of AF. since then, plenty studies have demonstrated that the PVs were not only important sources of the initiation of AF, but also played an important role in the maintenance of AF.Furthermore, previous clinical studies have shown that hypertension could lead to atrial dilatation and fibrosis. Increased stretch may modify the electrophysiological characteristics of cardiac tissue, thus make AF easier to maintain and has been shown to increase spontaneous electrical activity from PVs. However, most of previous studies on the associations between hypertension and AF have specifically focused on the atrium level. To date, there is a paucity of data regarding the arrhythmogenic role of PVs in the direct link between hypertension and AF.Objective:The purpose of this study was to identify whether electrophysiological and histological changes occur within the pulmonary veins in two-kidney, one-clip (2K1C) hypertensive rats.Methods:Male Sprague-Dawley (SD) rats (n=50,180-200g) were randomly allocated to 2K1C group (n=30) and sham-operated group (n=20). Tail systolic blood pressure (SBP) was assessed every 2 weeks. Rats were studied after 4 months. Left atrial diameter (LAD), diastolic interventricular septal thickness (IVS; d) and left ventricular ejection fraction (EF%) were measured by transthoracic echocardiography. Left superior pulmonary vein (LSPV) and left atrial fibrosis was evaluated in Masson trichrome-stain. Protein expression of fibrosis markers angiotensinⅡ (AngⅡ), transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), collagen I (Col I) and ion channel Kir2.1, Kir2.3, Cav1.2, Nav1.5 were quantified by Western blot on LSPV. Conventional microelectrodes were used to record action potential duration at 90% repolarization (APD90) and effective refractory period (ERP) in isolated LA.Results:At 4 months, hypertensive rats developed LA dilation (6.01±0.29 mm vs 4.78±0.51 mm). Collagen deposition in the LSPV and LA and expression of TGF-β1， MMP-2 and Col I in the LSPV were significantly increased in hypertensive rats. Additionally, hypertension reduced Nav1.5 and Kir2.1 expression, although there were no significant differences in APD90 and ERP and expression of AngⅡ, Kir2.3, Cav1.2 between the two groups.Conclusions:Hypertension is associated with electrophysiological and histological changes in the LSPV characterized by significantly reduced Nav1.5 and Kir2.1 expression and increasing interstitial fibrosis. Meanwhile, hypertension leads to LA enlargement and interstitial fibrosis. The remodelings of both LSPV and LA induced by hypertension provide substrates for AF to trigger and maintain. |
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