Bone mass loss in chronic heart failure is associated with sympathetic nerve activation

Zhiyuan Guan; Wanqiong Yuan; Jialin Jia; Chenggui Zhang; Junxiong Zhu; Jie Huang; Wang Zhang; Dongwei Fan; Huijie Leng; Zijian Li; Yingsheng Xu; Chunli Song

doi:10.1016/j.bone.2022.116596

Bone mass loss in chronic heart failure is associated with sympathetic nerve activation

Bone. 2023 Jan:166:116596. doi: 10.1016/j.bone.2022.116596. Epub 2022 Oct 25.

Authors

Affiliations

¹ Department of Orthopedics, Peking University Third Hospital, Beijing, China.
² Department of Orthopedics, Peking University Third Hospital, Beijing, China; Beijing Key Laboratory of Spinal Diseases, Beijing, China.
³ Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China.
⁴ Department of Neurology, Peking University Third Hospital, Beijing 100191, China.
⁵ Department of Orthopedics, Peking University Third Hospital, Beijing, China; Beijing Key Laboratory of Spinal Diseases, Beijing, China. Electronic address: schl@bjmu.edu.cn.

PMID: 36307018
DOI: 10.1016/j.bone.2022.116596

Abstract

Purpose: Chronic heart failure causes osteoporosis, but the mechanism remains unclear. The sympathetic nerve plays an important role in both bone metabolism and cardiovascular function.

Methods: Thirty-six adult male SD rats were randomly divided into the following four groups: sham surgery (Sham) group, guanethidine (GD) group, abdominal transverse aorta coarctation-induced heart failure + normal saline (TAC) group, and TAC + guanethidine (TAC + GD) group. Normal saline (0.9 % NaCl) or guanethidine (40 mg/kg/ml) was intraperitoneally injected daily for 5 weeks. Then, DXA, micro-CT, ELISA and RT-PCR analyses were performed 12 weeks after treatment.

Results: The bone loss in rats subjected to TAC-induced chronic heart failure and chemical sympathectomy with guanethidine was increased. Serum norepinephrine levels were increased in rats with TAC-induced heart failure but were decreased in TAC-induced heart failure rats treated with guanethidine. The expression of α2A adrenergic receptor, α2C adrenergic receptor, osteoprotegerin (OPG), and osteocalcin in the tibia decreased in the TAC-induced heart failure group, and the expression of β1 adrenergic receptor, β2 adrenergic receptor, receptor activator of nuclear factor-κ B ligand (RANKL), and RANKL/OPG in the tibia increased in the heart failure group. In addition, these changes in gene expression levels were rescued by chemical sympathectomy with guanethidine.

Conclusions: TAC-induced chronic heart failure is associated with bone mass loss, and the sympathetic nerve plays a significant role in heart failure-related bone mass loss.

Mini abstract: The present study supports the hypothesis that heart failure is related to bone loss, and the excessive activation of sympathetic nerves participates in this pathophysiological process. The present study suggests a potential pathological mechanism of osteoporosis associated with heart failure and new perspectives for developing strategies for heart failure-related bone loss.

Keywords: Guanethidine; Heart failure; Osteoporosis; Sympathetic nerve; β Adrenergic receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Guanethidine
Heart Failure* / complications
Male
Osteoporosis* / pathology
Osteoprotegerin / metabolism
RANK Ligand / metabolism
Rats
Rats, Sprague-Dawley
Saline Solution

Substances

Guanethidine
Osteoprotegerin
RANK Ligand
Saline Solution