Bone mechanical loading reduces heart rate and increases heart rate variability in mice.

Cardiovascular disease and osteoporosis are clinically associated. Bone adapts to mechanical forces by altering its overall structure and mass. In response to mechanical strain bone cells release signaling molecules and activate the nervous system. Bone also exhibits endocrine functions that modulate a number of tissues including the heart. We hypothesized that bone mechanical loading acutely alters cardiac function via neural and/or endocrine mechanisms. To test this hypothesis, we performed in vivo tibia mechanical loading in anesthetized mice while monitoring heart parameters using electrocardiogram (ECG). An immediate, transient reduction in resting heart rate was observed during tibial loading in both adult male and female mice ( < 0.01) with concurrent increases in heart rate variability (HRV) (p < 0.01). ECG intervals, PR, QRS and QTc were unaffected with loading. In further studies, we found that at least 3 N of load was necessary to elicit this heart response in adult mice. With aging to 11-12 months the responsiveness of the heart to loading was blunted, suggesting this bone-heart connection may weaken with age. Administration of lidocaine around the tibia significantly diminished the heart rate response to bone loading ( < 0.05). Moreover, pre-treatment with sympathetic antagonist propranolol inhibited this heart rate response to loading ( < 0.05), while parasympathetic antagonist atropine did not ( > 0.05). This suggests that a neuronal afferent pathway in the hindlimb and reduction in efferent sympathetic tone mediate this bone-neuro-heart reflex. In conclusion, the findings that tibia bone loading age-dependently modulates heart function support the concept of physiological coupling of the skeletal and cardiovascular systems.