Effects of renal denervation at BP-elevation/reduction sites guided by renal nerve stimulation on atrial neural and structural remodeling in a hypertensive canine model

Abstract

Hypertension is a common condition in cardiovascular medicine, and can lead to atrial enlargement, atrial fibrosis, and even the development of atrial fibrillation. Renal denervation (RDN) causes reduction in blood pressure (BP), but its effects on hypertension-related atrial remodeling remain unclear. This study aimed to explore the effects of RDN at BP-elevation/reduction sites guided by renal nerve stimulation (RNS) on atrial neural and structural remodeling in a hypertensive canine model. The twenty-four Chinese Kunming dogs were divided into three groups: (1) the reduced BP response ablation group (RRA group, n = 8), (2) the renal stimulation control group (RSC group, n = 8), and (3) the elevated BP response ablation group (ERA group, n = 8), which were followed for 4 weeks. Our results showed that in terms of atrial neural remodeling, compared with the RSC group, the ERA group exhibited reduced tyrosine hydroxylase (TH) protein expression and a lower TH/ choline acetyltransferase (ChAT) ratio. In contrast, the RRA group showed lower ChAT and muscarinic acetylcholine receptor 2 (CM2) protein expression, and an elevated TH/ChAT ratio. Compared with the RSC group, the ERA group presented a smaller myocyte area, reduced collagen I protein expression, and lower myocardial interstitial collagen fiber content. In contrast, the RRA group presented a larger myocyte area, increased collagen I protein expression, and greater collagen fiber content. Overall, RDN at elevated BP response sites improved atrial neural and structural remodeling under hypertensive conditions, whereas RDN at reduced BP response sites exacerbated the imbalance between atrial sympathetic and parasympathetic nerve activity and worsened structural remodeling.

Keywords: Atrial remodeling; Renal denervation; Renal nerve stimulation.