Oxygen carotid body

Chemoreceptors. The peripheral chemoreceptors include the carotid bodies, located at the bifurcation of the common carotid arteries, and the aortic bodies, located in the aortic arch. These receptors are stimulated by a decrease in arterial oxygen (hypoxia), an increase in arterial carbon dioxide (hypercapnia),... 

Administration of oxygen-rich gas mixtures is useful in hypoxia, but 100% 02 is not often used. In chronic bronchitis, hypoxia and hypercapnia coexist, the respiratory centre in the medulla becomes tolerant to the high C02 content of blood and is relatively insensitive to it. Respiratory drive is maintained by hypoxia acting via chemoreceptors in the aorta and carotid body. Removal of the hypoxic stimulus to the respiratory centre in the medulla may actually stop the patient breathing. 

Adiponitrile s mechanism of toxicity is similar to cyanide because it can potentially liberate cyanide in the body spontaneously. It forms a stable complex with ferric iron in the cytochrome oxidase enzymes, thereby inhibiting cellular respiration. Cyanide affects primarily the central nervous system (CNS), producing early stimulation followed by depression. It initially stimulates the peripheral chemoreceptors (causing increased respiration) and the carotid bodies (thereby slowing the heart). Early CNS, respiratory, and myocardial depression result in decreased oxygenation of the blood and decreased cardiac output. These effects produce both stagnation and hypoxemic hypoxia in addition to cytotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase. 

Lopez-Barneo J. 2003. Oxygen and glucose sensing by carotid body glomus cells. Curr Opin Neurobiol 13 493-499. 

A decrease below the threshold Pq, normally close to 50 Torr, in glomus cells of the carotid body or in the neonatal ductus arteriosus results in an inhibition of the tonic K current. Such oxygen-regulated inhibition of K+ channels, which may be mediated by mitochondria-derived hydrogen peroxide (Archer et al., 2004), results in an increase in cellular excitability, increased Ca + influx, and a resultant increase in the level of Ca + in the cytosol (reviewed by Lopez-Barneo et al., 1999). 

A schematic representation of how a decrease in oxygen tension (hypoxia) may affect carotid body glomus cell function. In the mitochondrial model, hypoxia affects either reactive oxygen species (ROS) production or ATP production of mitochondria. Both of these may affect the outward flux of potassium via the potassium channel with the downstream effects shown in the diagram. In the membrane model, the ROS production by membrane-bound molecules (cytochromes) is oxygen sensitive, and thereby affected by hypoxia. Thus, these membrane-bound molecules function as proximal oxygen sensors and cause effects on potassium channels with the downstream effects described in the figure and in the text... 

It has been known for some time that TH protein expression is oxygen sensitive and shows a graded response to the duration of hypoxic exposure in the rat medulla. A short 3-day exposure resulted in a 26— 50% increase in TH depending on the subpopulation of medullary nuclei examined. In contrast, 14 days of hypoxic exposure resulted in 31-41% increases in TH, after which the level of TH returned to baseline (Schmitt et ak, 1993). While oxygen sensors in the medulla appear to regulate the level of TH without input from the carotid body, the hypoxia-induced increase in turnover rate of noradrenaline (NE) requires input from the carotid body (Soulier et ak, 1992). 

Di Giulio C, Bianchi G, Cacchio M, Artese L, Piccirilli M, et al. 2006. Neuroglobin, a new oxygen binding protein is present in the carotid body and increases after chronic intermittent hypoxia. Berlin Springer-Verlag pp. 15-19. 

Donnelly DF. 1997. Are oxygen dependent K channels essential for carotid body chemo-transduction Resp Physiol 110 211-218,... 

Gonzitlez C, Lopez-Lopez JR, Obeso A, Perez-Garcia MT, Rocher A. 1995a. Cellular mechanisms of oxygen chemoreception in the carotid body. Resp Physiol 102 137-147. 

Gonzalez C, Vicario I, Almaraz L, Rigual R 1995b. Oxygen sensing in the carotid body. Biol Signals 4 245-256. 

Prabhakar NR, Overholt JL. 2000. Cellular mechanisms of oxygen sensing at the carotid body Heme proteins and ion channels. Respir Physiol 122 209-221. 

Wilson DF, Mokashi A, Chugh D, Vinogradov S, Osanai S, et al. 1994. The primary oxygen sensor of the cat carotid body is cytochrome of the mitochondrial respiratory chain. FEBS Lett 351 370-374. 

Chemoreceptors. Early investigators assumed that the chemically sensitive areas controlling respiration were located in the brain. In 1926 De Castro (15) suggested that the carotid bodies, located near the carotid bifurcation of each common carotid artery, also could be important chemoreceptors. Shortly thereafter, Heymans and Heymans (16) found that ventilation was stimulated when the aortic arch of an animal was perfused with blood from an animal breathing a low oxygen air mixture. This study established the existence and general location of chemosensi-tive bodies in the aortic arch (the aortic bodies). Additional studies by Heymans and co-workers (17) delineated the location and function of the carotid bodies and demonstrated that they were stimulated by hypoxia and hypercapnia. The exact location and function of the aortic bodies was described by Comroe (18). 

As for adrenaline at least, an interruption on the entire respiratory metabolism may be observed, which is reflected on the chemoceptors of the carotid body by the variations of oxygen uptake and carbon dioxide production (148). The direct intervention on the chemoceptors of the carotid and aortic bodies only appears for the nicotinic substances and not for Pervitin (149). The natural sympathomimetics which possess a stimulating influence on the respiration are mainly ephedrine, hordenine, 0-phenylethylamine, and tyramine. 

The rat carotid body possesses an NADPH oxidase, which shows certain properties similar to the ones of NADPH oxidase in neutrophils (Acker et al. 1989). NADPH oxidase of the carotid body has been suggested to play a role as sensor for the oxygen concentration in the arterial blood (Acker et al. 1989). The rat carotid body shows a typical spectrum of cytochrome b and diphenylene iodo-nium inhibits H2O2 formation (Cross et al. 1990). 

Figure 1 Tissue oxygen concentrations experienced by some mammalian cells. Values for the carotid body are from measurements of the carotid body microvasculature with an arterial PO2 of 145 iM, taken from Lahiri et al. (110). Values for brain are from measurements taken within many regions of the brain in rat, cat, rabbit, and piglet, reviewed in Erecinska and Silver (111). Liver PO2 measurements are from rat, taken from deGroot and Noll (112) and Vollmar and Menger (113). Measurements of heart ventricle are from the epicardium of ventricles in cat, dog, and piglet, taken from Rumsey et al. (114,115) and Honig and Gayeski (116). Tissue PO2 measurements reported in the literature were converted from units of torr to pM O2 using the conversion factor of 1.4 pM O2 per unit torr.

Fidone S, Gonzalez C, Yoshizaki K. Effects of low oxygen on the release of dopamine fi om the rabbit carotid body in vitro. J Physiol (Lend) 1982 333 93-110. 

Fishman MC, Greene WL, Platika D. Oxygen chemoreception by carotid body cells in culture. Proc Natl Acad Sci USA 1985 82 1448-1450. 

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