Carotid body chemoreceptors

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),... 

The peripheral chemoreceptors include the carotid and aortic bodies. The carotid bodies, which are more important in humans, are located near the bifurcation of the common carotid arteries. The aortic bodies are located in the arch of the aorta. The peripheral chemoreceptors respond to a decrease in P02/ an increase in PC02, and a decrease in pH (increase in H+ ion concentration) of the arterial blood. 

Results of in vitro studies suggest an interaction between calcium ions and cyanide in cardiovascular effects (Allen and Smith 1985 Robinson et al. 1985a). It has been demonstrated that exposure to cyanide in metabolically depleted ferret papillary muscle eventually results in elevated intracellular calcium levels, but only after a substantial contracture develops (Allen and Smith 1985). The authors proposed that intracellular calcium may precipitate cell damage and arrhythmias. The mechanism by which calcium levels are raised was not determined. Franchini and Krieger (1993) produced selective denervation of the aortic and carotid bifurcation areas, and confirmed the carotid body chemoreceptor origin of cardiovascular, respiratory and certain behavioral responses to cyanide in rats. Bradycardia and hyperventilation induced by cyanide are typical responses evoked by carotid body chemoreceptor stimulation (Franchini and Krieger 1993). 

Franchini KG, Krieger EM. 1993. Cardiovascular responses of conscious rats to carotid body chemoreceptor stimulation by intravenous KCN. J Auton Nerv Syst 42(l) 63-69. 

Chapter 28). Stimulation of nicotinic receptors in adrenergic nerve terminals leads to the release of norepinephrine and activation of nicotinic chemoreceptors in the aortic arch and carotid bodies causes nausea and vomiting. Nicotinic receptors in the central nervous system mediate a complex range of excitatory and inhibitory effects. 

Low doses of nicotine stimulate respiration through activation of chemoreceptors in the aortic arch and carotid bodies, while high doses directly stimulate the respiratory centers. In toxic doses, nicotine depresses respiration by inhibiting the respiratory centers in the brainstem and by a complex action at the receptors at the neuromuscular junction of the respiratory muscles. At these neuromuscular receptors, nicotine appears to occupy the receptors, and the end plate is depolarized. After this, the muscle accommodates and relaxes. These central and peripheral effects paralyze the respiratory muscles. 

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. 

C.N. Wyatt et al., 02-sensitive currents in carotid body chemoreceptor cells from normoxic and chronically hypoxic rats and their roles in hypoxic chemotransduction, Proc. Natl. Acad. Sci. USA 92(1995) 295-299. 

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. 

Doxapram (respiratory stimulant that activates peripheral aortic and carotid body chemoreceptors) behaves as a physiological antagonist when used to reverse central respiratory depression caused by barbiturates or inhalational anaesthetic agents. 

ATP has been implicated as a neurotransmitter in the peripheral chemoreceptors as a result of hypoxic (Prasad et al., 2001 Buttigieg and Nurse, 2004) and CO2/PH stimulation (Zhang and Nurse, 2004). ATP was presumed to be costored with other classical transmitters (e.g., ACh, dopamine, 5-HT, and GABA in the synaptic vesicles in the chemoreceptor cells (type 1 cells) of the carotid body) (Gonzalez et al., 1994 Zhang et al., 2000). More recently, a direct stimulus-evoked ATP release from the type-1 cells has been demonstrated (Buttigieg and Nurse, 2004), and this release was dependent on extracellular Ca via mainly L-type Ca + channels, blocked by nifedipine (50 pm) and cadmium (50 pm). 

After exposure of cats to normobaric hypero da for over 36 h, their carotid chemoreceptors did not respond to hypoxia but responded to hypercapnia with an overshoot and enhanced activity. The overshoot was abolished after inhibition of carbonic anhydrase with acetazolamide, showing that carotid body chemoreception responded to H+ (Lahiri et al., 1987). 

Buckler KJ, Vaughan-Jones RD. 1994. Role of intracellular pH and [Ca " "] in chemoreceptor cells of carotid body. In Arterial Chemoreceptors Cell to System, pp. 41-55. 

Buttigieg J, Nurse CA. 2004. Detection of hypoxia-evoked ATP release from chemoreceptor cells of the rat carotid body. Biochem Biophys Res Commun 322 82-87. 

Gonzalez C, Almaraz L, Obeso A, Rigual R. 1994. Carotid body chemoreceptors From natural stimuli to sensory discharges. Physiol Rev 74 829-898. 

Mulligan E, Lahiri S. 1982. Separation of carotid body chemoreceptor responses to O2 and CO2 by oligomycin and by antimycin A. Am J Physiol 242 C200-C206. 

Zhang M, Zhong H, Vollmer C, Nurse CA. 2000. Co-release of ATP and ACh mediates hypoxic signalling at rat carotid body chemoreceptors. J Physiol 525 143-158. 

Lahiri S, Acker H. 1999. Redox-dependent binding of CO to heme protein controls Poysensitive chemoreceptor discharge of the rat carotid body. Resp Physiol 115 169-177. 

Verna, A., Rowny, M., and Leitner, L.M., Loss of chemoreceptor properties of the rabbit carotid body after destruction of the glomus cells. Brain Res., 100, 13-23, 1975. 

Nicotine stimulates sensory receptors that respond to stretch or pressure of the skin, mesentery, tongue, lung and stomach chemoreceptors of the carotid body thermoreceptors of skin and tongue and pain receptors. 

Lahiri, S., Ehleben, W., and Acker, H., Chemoreceptor discharges and cytochrome redox changes of the rat carotid body Role of heme ligands. Proceedings of the National Academy of Science USA, 96, 9427, 1999. 

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). 

Nicotine, like ACh, will stimulate a number of sensory receptors. These include mechanore-ceptors that respond to stretch or pressure of the skin, mesentery, tongue, lung, and stomach chemoreceptors of the carotid body thermal receptors of the skin and tongue and pain receptors. Prior administration of hexamethonium prevents stirmilation of the sensory receptors by nicotine but has little, if any, effect on the activation of sensory receptors by physiological stimuli. 

In general, the cardiovascular responses to nicotine are due to stimulation of sympathetic ganglia and the adrenal medulla, together with the discharge of catecholamines from sympathetic nerve endings. Also contributing to the sympathomimetic response to nicotine is the activation of chemoreceptors of the aortic and carotid bodies, which reflexly results in vasoconstriction, tachycardia, and elevated blood pressure. 

The histological structure of the carotid bodies is very typical. The chemoreceptor cell contains unstable granules that disappear when the nerve endings of the carotid bodies are stimulated. The mechanism by which the chemical stimulus is converted to an electrical impulse is not known. Aortic chemoreceptors are found between the aortic arch and the pulmonary artery on the dorsal aspect of the pulmonary artery. 

The conclusion at this time is that, hypoxic and hypercapnic perfusion of the carotid body chemoreceptors produces transient reflex parasympathetic coronary vasodilation. The importance of this reflex parasympathetic control of coronary blood flow in overall coronary regulation remains to be determined. 

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