Electrical and histological remodeling of the pulmonary vein in 2K1C hypertensive rats: Indication of initiation and maintenance of atrial fibrillation.

OBJECTIVE

Hypertension is a significant risk factor for atrial fibrillation (AF). The role of pulmonary vein (PV) remodeling in the mechanistic association between hypertension and AF is not definitive. In this study, we aimed to identify changes in the electrophysiology and histology in PVs in two-kidney, one-clip (2K1C) hypertensive rats.

METHODS

Fifty male Sprague-Dawley rats were classified into the 2K1C and sham-operated groups. The systolic blood pressure was measured every 2 weeks. The left atrial diameter was measured by transthoracic echocardiography. Left superior PV (LSPV) and left atrial (LA) fibrosis was evaluated by Masson's trichrome staining. The expression of fibrosis markers [angiotensin II (Ang II), transforming growth factor-ß1 (TGF-ß1), matrix metalloproteinase-2 (MMP-2), and collagen I (Col I)] and ion channels [Kir2.1, Kir2.3, Cav1.2, and Nav1.5] in LSVP was quantified by western blot. Conventional microelectrodes were used to record the action potential duration at 90% repolarization (APD90) and effective refractory period (ERP) in isolated LA.

RESULTS

At 4 months, the 2K1C hypertensive rats developed LA dilation. Col deposition in LSPV and left atrium and expression of TGF-ß1, MMP-2, and Col I in LSPV were significantly increased in 2K1C hypertensive rats. In addition, hypertension reduced the expression of Nav1.5 and Kir2.1, although there were no significant differences in APD90; ERP; and expression of Ang II, Kir2.3, and Cav1.2 between the two groups.

CONCLUSION

Hypertension may lead to changes in the electrophysiology and histology of rats PVs, which is characterized by significant reduction in the expression of Nav1.5 and Kir2.1 and increase in interstitial fibrosis. These observations may clarify the role of PVs in the mechanistic association between hypertension and AF.