Role of Peripheral Chemoreceptors on Enhanced Central Chemoreflex Drive in Nonischemic Heart Failure.

Heart failure (HF) is a prevalent disease in elderly population. Potentiation of the ventilatory chemoreflex drive plays a pivotal role in disease progression, at least in part, through their contribution to the generation/maintenance of breathing disorders. Peripheral and central chemoreflexes are mainly regulated by carotid body (CB) and the retrotrapezoid nuclei (RTN), respectively. Recent evidence showed an enhanced central chemoreflex drive in rats with nonischemic HF along with breathing disorders. Importantly, increase activity from RTN chemoreceptors contribute to the potentiation of central chemoreflex response to hypercapnia. The precise mechanism driving RTN potentiation in HF is still elusive. Since interdependency of RTN and CB chemoreceptors has been described, we hypothesized that CB afferent activity is required to increase RTN chemosensitivity in the setting of HF. Accordingly, we studied central/peripheral chemoreflex drive and breathing disorders in HF rats with and without functional CBs (CB denervation). We found that CB afferent activity was required to increase central chemoreflex drive in HF. Indeed, CB denervation restored normal central chemoreflex drive and reduced the incidence of apneas by twofold. Our results support the notion that CB afferent activity plays an important role in central chemoreflex potentiation in rats with HF.

Enhanced Peripheral Chemoreflex Drive Is Associated with Cardiorespiratory Disorders in Mice with Coronary Heart Disease.

Coronary heart disease (CHD) is a prevalent cardiovascular disease characterized by coronary artery blood flow reductions caused by lipid deposition and oxidation within the coronary arteries. Dyslipidemia is associated with local tissue damage by oxidative stress/inflammation and carotid bodies (CB) peripheral chemoreceptors are heavily modulated by both reactive oxygen species and pro-inflammatory molecules (i.e., cytokines). Despite this, it is not know whether CB-mediated chemoreflex drive may be affected in CHD. In the present study, we evaluated peripheral CB-mediated chemoreflex drive, cardiac autonomic function, and the incidence of breathing disorders in a murine model of CHD. Compared to age-matched control mice, CHD mice showed enhanced CB-chemoreflex drive (twofold increase in the hypoxic ventilatory response), cardiac sympathoexcitation, and irregular breathing disorders. Remarkably, all these were closely linked to the enhanced CB-mediated chemoreflex drive. Our results showed that mice with CHD displayed an enhanced CB chemoreflex, sympathoexcitation, and disordered breathing and suggest that CBs may be involved in chronic cardiorespiratory alterations in the setting of CHD.