Carotid body chemoreceptors, sympathetic neural activation, and cardiometabolic disease

Abstract

The carotid body (CB) is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome.

Fig. 1

Carotid body mediates sympathoexcitation and oscillatory breathing patterns in heart failure. Representative recordings of tidal ventilation (Vt), renal sympathetic nerve activity (RSNA) and integrated RSNA (iSNA) in one control (sham–sham) animal, one chronic heart failure animal with intact carotid bodies (CHF–sham) and one chronic heart failure animal that underwent carotid body denervation (CHF–CBD). Note that CBD normalize RSNA and ventilatory oscillations. Reprinted from Marcus et al. [27] with permission of John Wiley and Sons

Fig. 2

Carotid Body denervation reduced myocardial fibrosis and cardiac arrhythmias and improved survival in heart failure rats. a Rats with chronic heart failure (CHF) and with CHF and carotid body denervation (eCBD) displayed tissue fibrosis in noninfarcted areas. The left ventricle (LV) freewall and the interventricular septum (IVS) obtained from CHF rats showed a marked collagen deposition. Selective eCBD significantly reduced cardiac fibrosis in the LV-freewall and in the IVS. b Representative tachograms showing arrhythmic episodes in a CHF rat and a marked decreased in the arrhythmic events in CHF+eCBD rat. c Rats that underwent eCBD showed reduced mortality rate compared to CHF rats with functional CBs. Modified from Del Rio et al. [10], with permission of Elsevier

Fig. 3

CIH increased basal carotid chemosensory discharges and induced a potentiation of chemosensory responses to acute hypoxia. The chemosensory responses to various levels of inspired O₂ (PO₂ ≈ 100−1 %) were measured from one carotid sinus nerve of a sham rat (a) and from a rat exposed to cyclic hypoxic episodes (PO₂ to 35 mmHg, 12 times per h during 8 h) for 21 days. (b) ƒ_csn, frequency of carotid chemosensory discharges expressed in Hz. Rats were anesthetized with sodium pentobarbitone (40 mg/kg ip) and breathed spontaneously room air. Reprinted from Iturriaga et al. [8] with permission of John Wiley and Sons