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Carotid Body Dysfunction and Mechanisms of Disease

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Morphofunctional and Neurochemical Aspects of the Mammalian Carotid Body

Abstract

Emerging evidence shows that the carotid body (CB) dysfunction is implicated in various physiological and pathophysiological conditions. It has been revealed that the CB structure and neurochemical profile alter in certain human sympathetic-related and cardiometabolic diseases. Specifically, a tiny CB with a decrease of glomus cells and their dense-cored vesicles has been seen in subjects with sleep disordered breathing such as sudden infant death syndrome and obstructive sleep apnea patients and people with congenital central hypoventilation syndrome. Moreover, the CB degranulation is accompanied by significantly elevated levels of catecholamines and proinflammatory cytokines in such patients. The intermittent hypoxia stimulates the CB, eliciting augmented chemoreflex drive and enhanced cardiorespiratory and sympathetic responses. High CB excitability due to blood flow restrictions, oxidative stress, alterations in neurotransmitter gases and disruptions of local mediators is also observed in congestive heart failure conditions. On the other hand, the morpho-chemical changes in hypertension include an increase in the CB volume due to vasodilation, altered transmitter phenotype of chemoreceptor cells and elevated production of neurotrophic factors. Accordingly, in both humans and animal models CB denervation prevents the breathing instability and lowers blood pressure. Knowledge of the morphofunctional aspects of the CB, a better understanding of its role in disease and recent advances in human CB translational research would contribute to the development of new therapeutic strategies.

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References

  • Abdala AP, McBryde FD, Marina N, Hendy EB, Engelman ZJ, Fudim M, Sobotka PA, Gourine AV, Paton JF (2012) Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat. J Physiol 590:4269–4277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams WE (1958) The comparative morphology of the carotid body and carotid sinus. Charles C Thomas Publisher, Springfield

    Google Scholar 

  • Atanasova DY, Lazarov NE (2014) Expression of neurotrophic factors and their receptors in the carotid body of spontaneously hypertensive rats. Respir Physiol Neurobiol 202:6–15

    Article  CAS  PubMed  Google Scholar 

  • Atanasova D, Dandov A, Dimitrov N, Lazarov NE (2018) Immunohistochemical localization of angiotensin AT1 receptors in the rat carotid body. Acta Histochem 120:154–158

    Article  CAS  PubMed  Google Scholar 

  • Atanasova DY, Dandov AD, Dimitrov ND, Lazarov NE (2020) Histochemical and immunohistochemical localization of nitrergic structures in the carotid body of spontaneously hypertensive rats. Acta Histochem 122:151500

    Article  CAS  PubMed  Google Scholar 

  • Atanasova DY, Dandov AD, Lazarov NE (2023) Neurochemical plasticity of the carotid body in hypertension. Anat Rec 306:2366–2377

    Google Scholar 

  • Baby SM, Gruber RB, Young AP, MacFarlane PM, Teppema LJ, Lewis SJ (2018) Bilateral carotid sinus nerve transection exacerbates morphine-induced respiratory depression. Eur J Pharmacol 834:17–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Badoer E (2020) The carotid body a common denominator for cardiovascular and metabolic dysfunction? Front Physiol 11:1069

    Article  PubMed  PubMed Central  Google Scholar 

  • Bardsley EN, Pen DK, McBryde FD, Ford AP, Paton JFR (2021) The inevitability of ATP as a transmitter in the carotid body. Auton Neurosci 234:102815

    Article  CAS  PubMed  Google Scholar 

  • Belaiba RS, Bonello S, Zähringer C, Schmidt S, Hess J, Kietzmann T, Görlach A (2007) Hypoxia up-regulates hypoxia-inducible factor-1α transcription by involving phosphatidylinositol 3-kinase and nuclear factor κB in pulmonary artery smooth muscle cells. Mol Biol Cell 18:4691–4697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caballero-Eraso C, Colinas O, Sobrino V, González-Montelongo R, Cabeza JM, Gao L, Pardal R, López-Barneo J, Ortega-Sáenz P (2023) Rearrangement of cell types in the rat carotid body neurogenic niche induced by chronic intermittent hypoxia. J Physiol 601:1017–1036

    Article  CAS  PubMed  Google Scholar 

  • Calverley PM (1999) Blood pressure, breathing, and the carotid body. Lancet 354:969–970

    Article  CAS  PubMed  Google Scholar 

  • Campanucci VA, Nurse CA (2007) Autonomic innervation of the carotid body: role in efferent inhibition. Respir Physiol Neurobiol 157:83–92

    Article  CAS  PubMed  Google Scholar 

  • Conde SV, Sacramento JF, Guarino MP (2018) Carotid body: a metabolic sensor implicated in insulin resistance. Physiol Genomics 50:208–214

    Article  CAS  PubMed  Google Scholar 

  • Conde SV, Polotsky VY, Joseph V, Kinkead R (2023) On the origins of sleep disordered breathing, cardiorespiratory and metabolic dysfunction: which came first, the chicken or the egg? J Physiol. https://doi.org/10.1113/JP284113

    Article  PubMed  Google Scholar 

  • Consolim-Colombo FM, Bortolotto LA (2018) Endothelium and arterial hypertension. In: Da Luz PL, Libby P, Chagas ACP, Laurindo FRM (eds) Endothelium and cardiovascular diseases: vascular biology and clinical syndromes, 1st edn. Academic Press, London, pp 429–437

    Chapter  Google Scholar 

  • Cutz E, Ma TK, Perrin DG, Moore AM, Becker LE (1997) Peripheral chemoreceptors in congenital central hypoventilation syndrome. Am J Respir Crit Care Med 155:358–363

    Article  CAS  PubMed  Google Scholar 

  • Del Rio R, Moya EA, Iturriaga R (2010) Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link. Eur Respir J 36:143–150

    Article  PubMed  Google Scholar 

  • Del Rio R, Munoz C, Arias P, Court FA, Moya EA, Iturriaga R (2011) Chronic intermittent hypoxia-induced vascular enlargement and VEGF upregulation in the rat carotid body is not prevented by antioxidant treatment. Am J Physiol Lung Cell Mol Physiol 301:L702–L711

    Article  PubMed  Google Scholar 

  • Del Rio R, Moya EA, Iturriaga R (2012) Contribution of inflammation on carotid body chemosensory potentiation induced by intermittent hypoxia. Adv Exp Med Biol 758:199–205

    Article  PubMed  Google Scholar 

  • Del Rio R, Marcus NJ, Schultz HD (2013) Carotid chemoreceptor ablation improves survival in heart failure: rescuing autonomic control of cardiorespiratory function. J Am Coll Cardiol 62:2422–2430

    Article  PubMed  Google Scholar 

  • Del Rio R, Andrade DC, Lucero C, Arias P, Iturriaga R (2016) Carotid body ablation abrogates hypertension and autonomic alterations induced by intermittent hypoxia in rats. Hypertension 68:436–445

    Article  PubMed  Google Scholar 

  • Fan J, Zhang B, Shu HF, Zhang XY, Wang X, Kuang F, Liu L, Peng ZW, Wu R, Zhou Z, Wang BR (2009) Interleukin-6 increases intracellular Ca2+ concentration and induces catecholamine secretion in rat carotid body glomus cells. J Neurosci Res 87:2757–2762

    Article  CAS  PubMed  Google Scholar 

  • Felippe ISA, Zera T, da Silva MP, Moraes DJA, McBryde F, Paton JFR (2023) The sympathetic nervous system exacerbates carotid body sensitivity in hypertension. Cardiovasc Res 119:316–331

    Article  CAS  PubMed  Google Scholar 

  • Fletcher EC, Lesske J, Behm R, Miller CC, Stauss H, Unger T (1992) Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea. J Appl Physiol 72:1978–1984

    Article  CAS  PubMed  Google Scholar 

  • Fung ML (2014) Pathogenic roles of the carotid body inflammation in sleep apnea. Mediators Inflamm 2014:354279

    Article  PubMed  PubMed Central  Google Scholar 

  • Fung ML (2015) Expressions of angiotensin and cytokine receptors in the paracrine signaling of the carotid body in hypoxia and sleep apnea. Respir Physiol Neurobiol 209:6–12

    Article  CAS  PubMed  Google Scholar 

  • Gao L, Ortega-Sáenz P, García-Fernández M, González-Rodríguez P, Caballero-Eraso C, López-Barneo J (2014) Glucose sensing by carotid body glomus cells: potential implications in disease. Front Physiol 5:398

    Article  PubMed  PubMed Central  Google Scholar 

  • Garvey JF, Taylor CT, McNicholas WT (2009) Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammation. Eur Respir J 33:1195–1205

    Article  CAS  PubMed  Google Scholar 

  • Gauda EB, Cristofalo E, Nunez J (2007) Peripheral arterial chemoreceptors and sudden infant death syndrome. Respir Physiol Neurobiol 157:162–170

    Article  CAS  PubMed  Google Scholar 

  • Gauda EB, Shirahata M, Masona A, Pichard LE, Kostuk EW, Chavez-Valdez R (2013) Inflammation in the carotid body during development and its contribution to apnea of prematurity. Respir Physiol Neurobiol 185:120–131

    Article  PubMed  Google Scholar 

  • Geertinger P (1978) The carotid body and schizophrenia. Schizophr Bull 4:16–18

    Article  CAS  PubMed  Google Scholar 

  • Gold OMS, Bardsley EN, Ponnampalam AP, Pauza AG, Paton JFR (2022) Cellular basis of learning and memory in the carotid body. Front Synaptic Neurosci 14:90231

    Article  Google Scholar 

  • Gozal D, Kheirandish-Gozal L (2008) Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. Am J Respir Crit Care Med 177:369–375

    Article  CAS  PubMed  Google Scholar 

  • Habeck JO (1991) Peripheral arterial chemoreceptors and hypertension. J Auton Nerv Syst 34:1–7

    Article  CAS  PubMed  Google Scholar 

  • Heath D, Smith P, Fitch R, Harris P (1985) Comparative pathology of the enlarged carotid body. J Comp Pathol 95:259–271

    Article  CAS  PubMed  Google Scholar 

  • Holgert H, Hökfelt T, Hertzberg T, Lagercrantz H (1995) Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome. Proc Natl Acad Sci USA 92:7575–7579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang J, Lusina S, Xie T, Ji E, Xiang S, Liu Y, Weiss JW (2009) Sympathetic response to chemostimulation in conscious rats exposed to chronic intermittent hypoxia. Respir Physiol Neurobiol 166:102–106

    Article  CAS  PubMed  Google Scholar 

  • Iturriaga R (2001) Nitric oxide and carotid body chemoreception. Biol Res 34:135–139

    Article  CAS  PubMed  Google Scholar 

  • Iturriaga R (2018) Translating carotid body function into clinical medicine. J Physiol 596:3067–3077

    Article  CAS  PubMed  Google Scholar 

  • Iturriaga R, Moya EA, Del Rio R (2009) Carotid body potentiation induced by intermittent hypoxia: implications for cardiorespiratory changes induced by sleep apnoea. Clin Exp Pharmacol Physiol 36:1197–1204

    Article  CAS  PubMed  Google Scholar 

  • Iturriaga R, Moya EA, Del Rio R (2015) Inflammation and oxidative stress during intermittent hypoxia: the impact on chemoreception. Exp Physiol 100:149–155

    Article  CAS  PubMed  Google Scholar 

  • Iturriaga R, Del Rio R, Idiaquez J, Somers VK (2016) Carotid body chemoreceptors, sympathetic neural activation, and cardiometabolic disease. Biol Res 49:13

    Article  PubMed  PubMed Central  Google Scholar 

  • Iturriaga R, Alcayaga J, Chapleau MW, Somers VK (2021) Carotid body chemoreceptors: physiology, pathology, and implications for health and disease. Physiol Rev 101:1177–1235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iturriaga R, Del Rio R, Alcayaga J (2022) Carotid body inflammation: role in hypoxia and in the anti-inflammatory reflex. Physiology 37:128–140

    Article  CAS  PubMed  Google Scholar 

  • Jansen AH, Ioffe S, Russell BJ, Chernick V (1981) Effect of carotid chemoreceptor denervation on breathing in utero and after birth. J Appl Physiol 51:630–633

    Article  CAS  PubMed  Google Scholar 

  • KÃ¥hlin J, Mkrtchian S, Ebberyd A, Hammarstedt-Nordenvall L, Nordlander B, Yoshitake T, Kehr J, Prabhakar P, Poellinger L, Fagerlund MJ, Eriksson LI (2014) The human carotid body releases acetylcholine, ATP and cytokines during hypoxia. Exp Physiol 99:1089–1098

    Article  PubMed  Google Scholar 

  • Kato K, Wakai J, Matsuda H, Kusakabe T, Yamamoto Y (2012) Increased total volume and dopamine β-hydroxylase immunoreactivity of carotid body in spontaneously hypertensive rats. Auton Neurosci 169:49–55

    Article  CAS  PubMed  Google Scholar 

  • Khan Q, Heath D, Nash J, Smith P (1989) Chronic carotid glomitis. Histopathology 14:471–481

    Article  CAS  PubMed  Google Scholar 

  • Kim LJ, Polotsky VY (2020) Carotid body and metabolic syndrome: mechanisms and potential therapeutic targets. Int J Mol Sci 21:5117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar P, Prabhakar NR (2012) Peripheral chemoreceptors: function and plasticity of the carotid body. Compr Physiol 2:141–219

    Article  PubMed  PubMed Central  Google Scholar 

  • Lam SY, Liu Y, Ng KM, Lau CF, Liong EC, Tipoe GL, Fung ML (2012) Chronic intermittent hypoxia induces local inflammation of the rat carotid body via functional upregulation of proinflammatory cytokine pathways. Histochem Cell Biol 137:303–317

    Article  CAS  PubMed  Google Scholar 

  • Lambermont B, Davenne E, Maclot F, Delvenne P (2021) SARS-CoV-2 in carotid body. Intensive Care Med 47:342–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lataro RM, Moraes DJA, Gava FN, Omoto ACM, Silva CAA, Brognara F, Alflen L, Brazão V, Colato RP, do Prado JC Jr, Ford AP, Salgado HC, Paton JFR (2023) P2X3 receptor antagonism attenuates the progression of heart failure. Nat Commun 14:1725

    Google Scholar 

  • Lazarov N, Atanasova D (2012) The human carotid body in health and disease. Acta Morphol Anthropol 19:135–140

    Google Scholar 

  • Lazarov N, Atanasova D (2019) Morphological and new neurochemical aspects of the mammalian carotid body. Trakia J Sci 17(Suppl. 2):67–72

    Article  Google Scholar 

  • Li Y-L, Li Y-F, Liu D, Cornish KG, Patel KP, Zucker IH, Channon KM, Schultz HD (2005) Gene transfer of neuronal nitric oxide synthase to carotid body reverses enhanced chemoreceptor function in heart failure rabbits. Circ Res 97:260–267

    Article  CAS  PubMed  Google Scholar 

  • Li YL, Xia XH, Zheng H, Gao L, Li YF, Liu D, Patel KP, Wang W, Schultz HD (2006) Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits. Cardiovasc Res 71:129–138

    Article  CAS  PubMed  Google Scholar 

  • Li HP, Wang HQ, Li N, Zhang L, Li SQ, Yan YR, Lu HH, Wang Y, Sun XW, Lin YN, Zhou JP, Li QY (2021) Model for identifying high carotid body chemosensitivity in patients with obstructive sleep apnea. Nat Sci Sleep 13:493–501

    Article  PubMed  PubMed Central  Google Scholar 

  • Li X, Zhu L-j, Lv J, Cao X (2023) Purinoceptor: a novel target for hypertension. Purinergic Signal 19:185–197

    Article  CAS  PubMed  Google Scholar 

  • López-Barneo J (2022) Neurobiology of the carotid body. Handb Clin Neurol 188:73–102

    Article  PubMed  Google Scholar 

  • López-Barneo J, Ortega-Sáenz P, González-Rodriguez P, Fernández-Agüera MC, Macías D, Pardal R, Gao L (2016) Oxygen sensing by arterial chemoreceptors: mechanisms and medical translation. Mol Aspects Med 47–48:90–108

    Article  PubMed  Google Scholar 

  • Machado RH, Paton JFR (2021) Relevance of carotid bodies in COVID-19: a hypothetical viewpoint. Auton Neurosci 233:102810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mansukhani MP, Wang S, Somers VK (2015) Chemoreflex physiology and implications for sleep apnoea: insights from studies in humans. Exp Physiol 100:130–135

    Article  PubMed  Google Scholar 

  • McBryde FD, Abdala AP, Hendy EB, Pijacka W, Marvar P, Moraes DJ, Sobotka PA, Paton JF (2013) The carotid body as a putative therapeutic target for the treatment of neurogenic hypertension. Nat Commun 4:2395

    Article  PubMed  Google Scholar 

  • Moya EA, Alcayaga J, Iturriaga R (2012) NO modulation of carotid body chemoreception in health and disease. Respir Physiol Neurobiol 184:158–164

    Article  CAS  PubMed  Google Scholar 

  • Naeye RL, Fisher R, Ryser M, Whalen P (1976) Carotid body in the sudden infant death syndrome. Science 191:567–569

    Article  CAS  PubMed  Google Scholar 

  • Najjar S, Pahlajani S, De Sanctis V, Stern JNH, Najjar A, Chong D (2017) Neurovascular unit dysfunction and blood–brain barrier hyperpermeability contribute to schizophrenia neurobiology: a theoretical integration of clinical and experimental evidence. Front Psychiatry 8:83

    Article  PubMed  PubMed Central  Google Scholar 

  • Niewinski P, Janczak D, Rucinski A, Tubek S, Engelman ZJ, Piesiak P, Jazwiec P, Banasiak W, Fudim M, Sobotka PA, Javaheri S, Hart ECJ, Paton JFR, Ponikowski P (2017) Carotid body resection for sympathetic modulation in systolic heart failure: results from first-in-man study. Eur J Heart Fail 19:391–400

    Article  PubMed  Google Scholar 

  • Ortega-Sáenz P, López-Barneo J (2020) Physiology of the carotid body: from molecules to disease. Annu Rev Physiol 82:127–149

    Article  PubMed  Google Scholar 

  • Ottestad W, Seim M, Mæhlen JO (2020) COVID-19 with silent hypoxemia. Tidsskr nor Laegeforen 140:1–3

    Google Scholar 

  • Paton JFR, Sobotka PA, Fudim M, Engelman ZJ, Hart EC, McBryde FD, Abdala AP, Marina N, Gourine AV, Lobo M, Patel N, Burchell A, Ratcliffe L, Nightingale A (2013) The carotid body as a therapeutic target for the treatment of sympathetically mediated diseases. Hypertension 61:5–13

    Article  CAS  PubMed  Google Scholar 

  • Pávai Z, Töro K, Keller E, Jung J (2005) Morphometric investigation of carotid body in sudden infant death syndrome. Rom J Morphol Embryol 46:93–97

    PubMed  Google Scholar 

  • Peng Y, Prabhakar NR (2004) Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity. J Appl Physiol 96:1236–1242

    Article  PubMed  Google Scholar 

  • Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR (2003) Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci USA 100:10073–10078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perrin DG, Cutz E, Becker LE, Bryan AC (1984a) Ultrastructure of carotid bodies in sudden infant death syndrome. Pediatrics 73:646–651

    Article  CAS  PubMed  Google Scholar 

  • Perrin DG, Cutz E, Becker LE, Bryan AC, Madapallimatum A, Sole MJ (1984b) Sudden infant death syndrome: increased carotid-body dopamine and noradrenaline content. Lancet 2:535–537

    Article  CAS  PubMed  Google Scholar 

  • Pijacka W, Katayama PL, Salgado HC, Lincevicius GS, Campos RR, McBryde FD, Paton JFR (2018) Variable role of carotid bodies in cardiovascular responses to exercise, hypoxia and hypercapnia in spontaneously hypertensive rats. J Physiol 596:3201–3216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Porzionato A, Macchi V, Guidolin D, Parenti A, Ferrara SD, De Caro R (2005) Histopathology of carotid body in heroin addiction. Possible chemosensitive impairment. Histopathology 46:296–306

    Article  CAS  PubMed  Google Scholar 

  • Porzionato A, Macchi V, De Caro R, Di Giulio C (2013a) Inflammatory and immunomodulatory mechanisms in the carotid body. Respir Physiol Neurobiol 187:31–40

    Article  CAS  PubMed  Google Scholar 

  • Porzionato A, Macchi V, Stecco C, De Caro R (2013b) The carotid body in sudden infant death syndrome. Respir Physiol Neurobiol 185:194–201

    Article  PubMed  Google Scholar 

  • Porzionato A, Emmi A, Stocco E, Barbon S, Boscolo-Berto R, Macchi V, De Caro R (2020) The potential role of the carotid body in COVID-19. Am J Physiol Lung Cell Mol Physiol 19:L620–L626

    Article  Google Scholar 

  • Porzionato A, Emmi A, Contran M, Stocco E, Riccetti S, Sinigaglia A, Macchi V, Barzon L, De Caro R (2021) Case report: the carotid body in COVID-19: histopathological and virological analyses of an autopsy case series. Front Immunol 12:736529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prabhakar NR (1999) NO and CO as second messengers in oxygen sensing in the carotid body. Respir Physiol 115:161–168

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR, Peng YJ (2004) Peripheral chemoreceptors in health and disease. J Appl Physiol 96:359–366

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR, Semenza GL (2012) Gaseous messengers in oxygen sensing. J Mol Med (Berl) 90:265–272

    Article  CAS  PubMed  Google Scholar 

  • Prabhakar NR, Peng YJ, Yuan G, Nanduri J (2018) Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia. Cell Tissue Res 372:427–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prabhakar NR, Peng YJ, Nanduri J (2023) Carotid body hypersensitivity in intermittent hypoxia and obtructive sleep apnea. J Physiol. https://doi.org/10.1113/JP284111

    Article  PubMed  Google Scholar 

  • Przybylski J, Janicki P, Trzebski A (1990) The increased catecholamine content in the carotid bodies of spontaneously hypertensive rats. In: Acker H, Trzebski A, O’Regan RG (eds) Chemoreceptors and chemoreceptor reflexes. Springer, Boston, pp 363–376

    Chapter  Google Scholar 

  • Radu G, Luca C, Petrescu L, Bordejevic DA, Tomescu MC, Andor M, Cîtu I, Mavrea A, Buda V, Tomescu C, Borcan F, Dehelean L (2020) The predictive value of endothelial inflammatory markers in the onset of schizophrenia. Neuropsychiatr Dis Treat 16:545–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribeiro MJ, Sacramento JF, González C, Guarino MP, Monteiro EC, Conde SV (2013) Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets. Diabetes 62:2905–2916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schultz HD, Del Rio R, Ding Y, Marcus NJ (2012) Role of neurotransmitter gases in the control of the carotid body in heart failure. Resp Physiol Neurobiol 184:197–203

    Article  CAS  Google Scholar 

  • Schultz HD, Marcus NJ, Del Rio R (2013) Role of the carotid body in the pathophysiology of heart failure. Curr Hypertens Rep 15:356–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schultz HD, Marcus NJ, Del Rio R (2015) Mechanisms of carotid body chemoreflex dysfunction during heart failure. Exp Physiol 100:124–129

    Article  PubMed  PubMed Central  Google Scholar 

  • Schulz E, Gori T, Münzel T (2011) Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res 34:665–673

    Article  CAS  PubMed  Google Scholar 

  • Shin MK, Yao Q, Jun JC, Bevans-Fonti S, Yoo DY, Han W, Mesarwi O, Richardson R, Fu Y-Y, Pasricha PJ, Schwartz AR, Shirahata M, Polotsky VY (2014) Carotid body denervation prevents fasting hyperglycemia during chronic intermittent hypoxia. J Appl Physiol 117:765–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin MK, Mitrut R, Gu C, Kim LJ, Yeung BHY, Lee R, Pham L, Tang WY, Sham JSK, Cui H, Polotsky VY (2021) Pharmacological and genetic blockade of TRPM7 in the carotid body treats obesity-induced hypertension. Hypertension 78:104–114

    Article  CAS  PubMed  Google Scholar 

  • Shu HF, Wang BR, Wang SR, Yao W, Huang HP, Zhou Z, Wang X, Fan J, Wang T, Ju G (2007) IL-1β inhibits IK and increases [Ca2+]i in the carotid body glomus cells and increases carotid sinus nerve firings in the rat. Eur J Neurosci 25:3638–3647

    Article  PubMed  Google Scholar 

  • Sinski M, Lewandowski J, Przybylski J, Bidiuk J, Abramczyk P, Ciarka A, Gaciong Z (2012) Tonic activity of carotid body chemoreceptors contributes to the increased sympathetic drive in essential hypertension. Hypertens Res 35:487–491

    Article  CAS  PubMed  Google Scholar 

  • Smith CA, Nakayama H, Dempsey JA (2003) The essential role of carotid body chemoreceptors in sleep apnea. Can J Physiol Phramacol 81:774–779

    Article  CAS  Google Scholar 

  • Sohn CS, Chang JW, George B, Chen S, Ramchandra R (2022) Role of the angiotensin type 1 receptor in modulating the carotid chemoreflex in an ovine model of renovascular hypertension. J Hypertens 40:1421–1430

    Article  CAS  PubMed  Google Scholar 

  • Stocco E, Barbon S, Tortorella C, Macchi V, De Caro R, Porzionato A (2020) Growth factors in the carotid body—an update. Int J Mol Sci 21:E7267

    Article  Google Scholar 

  • Sweetland GD, Eggleston C, Bartz JC, Mathiason CK, Kincaid AE (2023) Expression of the cellular prion protein by mast cells in the human carotid body. Prion 17:67–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi M, Matsuda H, Hayashida Y, Yamamoto Y, Tsukuda M, Kusakabe T (2011) Morphological characteristics and peptidergic innervation in the carotid body of spontaneously hypertensive rats. Histol Histopathol 26:369–375

    PubMed  Google Scholar 

  • Toledo C, Andrade DC, Lucero C, Schultz HD, Marcus N, Retamal M, Madrid C, Del Rio R (2017) Contribution of peripheral and central chemoreceptors to sympatho-excitation in heart failure. J Physiol 595:43–51

    Article  CAS  PubMed  Google Scholar 

  • Vennemann MM, Loddenkötter B, Fracasso T, Mitchell EA, Debertin AS, Larsch KP, Sperhake JP, Brinkmann B, Sauerland C, Lindemann M, Bajanowski T (2012) Cytokines and sudden infant death. Int J Leg Med 126:279–284

    Article  Google Scholar 

  • Villadiego J, Ramírez-Lorca R, Cala F, Labandeira-García JL, Esteban M, Toledo-Aral JJ, López-Barneo J (2021) Is carotid body infection responsible for silent hypoxemia in COVID-19 patients? Function (Oxf) 2:zqaa032

    Google Scholar 

  • Xue F, Liu L, Fan J, He S, Li R, Peng ZW, Wang BR (2015) Interleukin-1β promotes the neurogenesis of carotid bodies by stimulating the activation of ERK1/2. Respir Physiol Neurobiol 219:78–84

    Article  CAS  PubMed  Google Scholar 

  • Zapata P, Larraín C, Reyes P, Fernández R (2011) Immunosensory signalling by carotid body chemoreceptors. Respir Physiol Neurobiol 178:370–374

    Article  CAS  PubMed  Google Scholar 

  • Zera T, Moraes DJA, Silva MD, Fisher JP, Paton JFR (2019) The logic of carotid body connectivity to the brain. Physiology 34:264–282

    Article  CAS  PubMed  Google Scholar 

  • Zhang XJ, Wang X, Xiong LZ, Fan J, Duan XL, Wang BR (2007) Up-regulation of IL-1 receptor type I and tyrosine hydroxylase in the rat carotid body following intraperitoneal injection of IL-1β. Histochem Cell Biol 128:533–540

    Article  CAS  PubMed  Google Scholar 

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Lazarov, N.E., Atanasova, D.Y. (2023). Carotid Body Dysfunction and Mechanisms of Disease. In: Morphofunctional and Neurochemical Aspects of the Mammalian Carotid Body. Advances in Anatomy, Embryology and Cell Biology, vol 237. Springer, Cham. https://doi.org/10.1007/978-3-031-44757-0_8

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