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

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.