Xiao-Qing-Long-Tang Maintains Cardiac Function during Heart Failure with Reduced Ejection Fraction in Salt-Sensitive Rats by Regulating the Imbalance of Cardiac Sympathetic Innervation.

Zhaoyu Li,Dufang Ma,Guofeng Zhou,Feng Dong,Yongcheng Wang,Yuehua Jiang,Ping Jiang,Yimei Zhang,Hengyi Zhao,Xiao Li,Jinlong Yang,Mohammed S Ali Shtayeh

doi:10.1155/2020/9467271

Abstract

Objective The anatomical and functional imbalances of sympathetic nerves are associated with cardiovascular disease progression. Xiao-Qing-Long-Tang (XQLT), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia for thousands of years. We determined the effect of XQLT in maintaining cardiac function during heart failure with reduced ejection fraction (HFrEF) with respect to its neurobiological effects in salt-sensitive rats. Methods Dahl salt-sensitive (DS) rats were fed a high-salt diet to establish an HFrEF model and were divided into model (DS, administered normal saline) and XQL groups (administrated XQLT) randomly, with SS-13BN rats being used as the control. The bodyweight and blood pressure of rats were observed regularly. Electrocardiogram, echocardiography, and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined to assess cardiac function. The sympathetic tune and myocardial morphological changes were evaluated. Western blot and qRT-PCR were used to assay the expression of the nerve growth factor (NGF) and leukemia inhibitory factor (LIF). Tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43) were assayed to confirm sympathetic remodeling. The micromorphological changes in cardiac sympathetic nerve endings were observed by transmission electron microscopy. Results Four weeks after XQLT treatment, cardiac function and bodyweight were higher and blood pressure was lower than that of the DS group. Myocardial noradrenaline (NA) increased, while the plasma NA level decreased significantly. The morphology demonstrated that XQLT significantly alleviated myocardial damage. XQLT decreased the expression of LIF, increased the expression of NGF, enhanced the TH+/GAP43+ and TH+/CHAT + positive nerve fiber density, and improved the TH and GAP43 protein expression, but had no effect on CHAT. Moreover, XQLT improved the micromorphology of sympathetic nerve endings in the myocardium. Conclusion XQLT maintains cardiac function during HFrEF in salt-sensitive rats, in part, by regulating the imbalance of cardiac sympathetic innervation.

Highlights

Cardiac sympathetic activation is an important biological feature of heart failure (HF) [1]
Our previous studies found that reversing sympathetic remodeling and maintaining sympathetic-vagal balance reduced the damage of sympathetic nerves and myocardium in diabetic rats [6, 7]. erefore, the treatment of heart failure with reduced ejection fraction (HFrEF) should not emphasize the inhibition of sympathetic nerves and should aim at restoring the sympathetic innervation balance
We focused on the imbalance of cardiac sympathetic innervation and aimed to explore the mechanism underlying the cardiac sympathetic innervation in rats with HFrEF. e data suggested that XQLT could maintain cardiac function in salt-sensitive rats with HFrEF by regulating the imbalance of nerve growth factor (NGF) and leukemia inhibitory factor (LIF)

Summary

Introduction

Cardiac sympathetic activation is an important biological feature of heart failure (HF) [1]. When HF occurs, the neuroendocrine system compensates, and the sympathetic and parasympathetic activities are unbalanced, which in turn promote cardiac compensatory remodeling and development of heart failure with reduced ejection fraction (HFrEF) [2, 3]. Reversing sympathetic remodeling is of great significance for the treatment of HFrEF. Our previous studies found that reversing sympathetic remodeling and maintaining sympathetic-vagal balance reduced the damage of sympathetic nerves and myocardium in diabetic rats [6, 7]. Erefore, the treatment of HFrEF should not emphasize the inhibition of sympathetic nerves and should aim at restoring the sympathetic innervation balance Our previous studies found that reversing sympathetic remodeling and maintaining sympathetic-vagal balance reduced the damage of sympathetic nerves and myocardium in diabetic rats [6, 7]. erefore, the treatment of HFrEF should not emphasize the inhibition of sympathetic nerves and should aim at restoring the sympathetic innervation balance

Methods

Results

Conclusion