Carotid body chemoreceptors: physiology, pathology, and implications for health and disease.

Published on Jul 1, 2021in Physiological Reviews37.312
· DOI :10.1152/PHYSREV.00039.2019
Rodrigo Iturriaga33
Estimated H-index: 33
,
Julio Alcayaga20
Estimated H-index: 20
+ 1 AuthorsVirend K. Somers118
Estimated H-index: 118
Source
Abstract
The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2, and pH, eliciting reflex ventilatory, cardiovascular and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiologic responses, and its role in maintaining health and potentiating disease. Emphasis will be placed on: i) Transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ionic channels; ii) Synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; iii) Integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and iv) The contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension and metabolic diseases, and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.
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#1Estelle B. GaudaH-Index: 27
#2Silvia V. Conde (NSU: Nova Southeastern University)H-Index: 19
Last. Nikola Despotovic (U of T: University of Toronto)H-Index: 1
view all 7 authors...
Obesity is a global epidemic in developed countries accounting for many of the metabolic and cardiorespiratory morbidities that occur in adults. These morbidities include type 2 diabetes, sleep-disordered breathing (SDB), obstructive sleep apnea, chronic intermittent hypoxia, and hypertension. Leptin, produced by adipocytes, is a master regulator of metabolism and of many other biological functions including central and peripheral circuits that control breathing. By binding to receptors on cells...
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#1Joao P. Cunha-Guimaraes (NOVA: Universidade Nova de Lisboa)H-Index: 2
#2Maria P. Guarino (IPN: Instituto Politécnico Nacional)H-Index: 18
Last. Silvia V. Conde (NOVA: Universidade Nova de Lisboa)H-Index: 19
view all 10 authors...
OBJECTIVE: The carotid bodies (CB) are peripheral chemoreceptor organs classically described as being O2 sensors, which are increasingly emerging as core players in metabolic control. Herein we evaluated CB activity in prediabetes patients and determined its correlation with dysmetabolism clinical features. DESIGN AND METHODS: Prediabetes patients were recruited at the Cardiology Service, Hospital Santa Marta, Centro Hospitalar Lisboa Central, EPE (CHLC-EPE). The study was approved by CHLC-EPE a...
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The carotid body (CB) is an arterial chemoreceptor organ located in the carotid bifurcation and has a well-recognized role in cardiorespiratory regulation. The CB contains neurosecretory sensory ce...
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#1Alejandro Moreno-Domínguez (University of Seville)H-Index: 2
#2Patricia Ortega-Sáenz (University of Seville)H-Index: 24
Last. José López-Barneo (University of Seville)H-Index: 60
view all 12 authors...
Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brainstem respiratory center. The mechanism by which changes in O2 tension modulate ion channels has remained elusive. Glomus cells express genes encoding HIF2α (Epas1) and atypical mit...
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Rationale: Obesity leads to resistant hypertension and mechanisms are poorly understood, but high plasma levels of leptin have been implicated. Leptin increases blood pressure acting both centrally...
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#2Elena Olea (CSIC: Spanish National Research Council)H-Index: 10
Last. Silvia V. Conde (NOVA: Universidade Nova de Lisboa)H-Index: 19
view all 9 authors...
KEY POINTS: Adenosine and ATP are excitatory neurotransmitters involved in the carotid body (CB) response to hypoxia. During ageing the CB exhibits a decline in its functionality, demonstrated by decreased hypoxic responses. In aged rats (20-24 months old) there is a decrease in: basal and hypoxic release of adenosine and ATP from the CB; expression of adenosine and ATP receptors in the petrosal ganglion; carotid sinus nerve (CSN) activity in response to hypoxia; and ventilatory responses to isc...
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#2Davi J. A. Moraes (USP: University of São Paulo)H-Index: 18
Last. Julian F. R. Paton (University of Auckland)H-Index: 79
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The carotid body has emerged as a therapeutic target for cardio-respiratory-metabolic diseases. With the expansive functions of the chemoreflex, we sought mechanisms to explain differential control...
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#1Lin Gao (University of Seville)H-Index: 19
#2Patricia Ortega-Sáenz (University of Seville)H-Index: 24
Last. José López-Barneo (University of Seville)H-Index: 60
view all 3 authors...
Abstract Acute oxygen sensing is essential for humans under hypoxic environments or pathologic conditions. This is achieved by the carotid body (CB), the key arterial chemoreceptor, along with other peripheral chemoreceptor organs, such as the adrenal medulla (AM). Although it is widely accepted that inhibition of K+ channels in the plasma membrane of CB cells during acute hypoxia results in the activation of cardiorespiratory reflexes, the molecular mechanisms by which the hypoxic signal is det...
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Cited By2
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#1Peter D. Wagner (UCSD: University of California, San Diego)H-Index: 108
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#1Andrea Porzionato (UNIPD: University of Padua)H-Index: 44
#2Aron Emmi (UNIPD: University of Padua)H-Index: 3
Last. Raffaele De Caro (UNIPD: University of Padua)H-Index: 44
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Various authors have hypothesized carotid body (CB) involvement in Coronavirus Disease 2019 (COVID-19), through direct invasion or indirect effects by systemic stimuli (‘cytokine storm’, angiotensin-converting enzyme [ACE]1/ACE2 imbalance). However, empirical evidence is limited or partial. Here, we present an integrated histopathological and virological analysis of CBs sampled at autopsy from four subjects (2 males and 2 females; age: >70 years old) who died of COVID-19. Histopathological, immu...
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#1Esteban Díaz-Jara (UC: Pontifical Catholic University of Chile)H-Index: 3
#2Hugo S. Díaz (UC: Pontifical Catholic University of Chile)H-Index: 8
Last. Fernando C. Ortiz (Autonomous University of Chile)H-Index: 9
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Abstract null null Enhanced central chemoreflex drive and irregular breathing are both hallmarks in heart failure (HF) and closely related to disease progression. Central chemoreceptor neurons located within the retrotrapezoid nucleus (RTN) are known to play a role in breathing alterations in HF. It has been shown that exercise (EX) effectively reduced reactive oxygen species (ROS) in HF rats. However, the link between EX and ROS, particularly at the RTN, with breathing alterations in HF has not...
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#1M. J. Olivares (Usach: University of Santiago, Chile)H-Index: 1
#2A Flores (Usach: University of Santiago, Chile)
Last. Jaime Eugenín (Usach: University of Santiago, Chile)H-Index: 18
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Abstract null null Central respiratory chemoreceptors play a key role in the respiratory homeostasis by sensing CO2 and H+ in brain and activating the respiratory neural network. This ability of specific brain regions to respond to acidosis and hypercapnia is based on neuronal and glial mechanisms. Several decades ago, glutamatergic transmission was proposed to be involved as a main mechanism in central chemoreception. However, a complete identification of mechanism has been elusive. At the rost...
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