Chronic hypoxia-induced morphological and neurochemical changes in the carotid body

Microscopy Research and Technique

Volumn 59, Issue 3, 2002, Pages 168-177

  Wang, Zun Yi ^a,b   Bisgard, Gerald E ^b  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

Adenosine triphosphate; Angiogenesis; Apoptosis; Dopamine; Endothelin; Hypertrophy; Mitosis; Nitric oxide; norepinephrine; Substance P; Vascular endothelial growth factor; Vasodilation

Indexed keywords

ADENOSINETRIPHOSPHATE; AMINES; AMINO ACIDS; BLOOD VESSELS; CELL DEATH; ENDOTHELIAL CELLS; NEUROPHYSIOLOGY; NOREPINEPHRINE; PATHOLOGY; PHOSPHATES;

ADENOSINE TRIPHOSPHATE; ANGIOGENESIS; CAROTID BODY; DOPAMINE; ENDOTHELIN; HYPERTROPHY; MITOSIS; SUBSTANCE-P; VASCULAR ENDOTHELIAL GROWTH FACTOR; VASODILATION;

NITRIC OXIDE;

ACETYLCHOLINE; ADENOSINE TRIPHOSPHATE; ATRIAL NATRIURETIC FACTOR; CALCITONIN GENE RELATED PEPTIDE; CATECHOLAMINE; CHOLECYSTOKININ; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; DNA; DOPAMINE; ENDOTHELIN; ENKEPHALIN; GALANIN; MESSENGER RNA; NEUROKININ 1 RECEPTOR; NEUROPEPTIDE Y; NITRIC OXIDE; NORADRENALIN; SEROTONIN; SUBSTANCE P; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; BLOOD VESSEL; CAROTID BODY; CAROTID BODY CHEMORECEPTOR; CHEMORECEPTOR; DNA SYNTHESIS; DOPAMINERGIC SYSTEM; HYPERTROPHY; HYPOXIA; INNERVATION; MITOSIS; NEUROCHEMISTRY; NEUROTRANSMISSION; NEWBORN; NONHUMAN; PRIORITY JOURNAL; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; VASODILATATION;

ANIMALIA;

EID: 0036827980     PISSN: 1059910X     EISSN: None     Source Type: Journal    
DOI: 10.1002/jemt.10191     Document Type: Article

References (116)

1. Aaron EA, Powell FL. 1993. Effect of chronic hypoxia on hypoxic ventilatory response in awake rats. J Appl Physiol 74:1635-1640.
2. Abramovici A, Pallot DJ, Polak JM. 1991. Immunohistochemical approach to the study of the cat carotid body. Acta Anat 14:70-74.
3. Abudara V, Eyzaguirre C. 1994. Electrical coupling between cultured glomus cells of the rat carotid body: Observations with current and voltage clamping. Brain Res 664:2257-2265.
4. Abudara V, Eyzaguirre C. 1996. Effects of hypoxia on the intercellular channel activity of cultured glomus cells. Adv Exp Med Biol 410: 151-158.
5. Abudara V, Eyzaguirre C, Saez JC. 2000. Short- and long-term regulation of rat carotid body gap junctions by cAMP. Identification of connexin43, a gap junction subunit. Adv Exp Med Biol 475:359-369.
6. Barnard P, Andronikou S, Pokorski M, Smatresk N, Mokashi A, Lahiri S. 1987. Time-dependent effect of hypoxia on carotid body chemosensory function. J Appl Physiol 63:685-691.
7. Bee D, Pallot DJ. 1995. Acute hypoxic ventilation, carotid body cell division, and dopamine content during early hypoxia in rats. J Appl Physiol 79:1504-1511.
8. Bee D, Pallot DJ, Barer GR. 1986. Division of type I and endothelial cells in the hypoxic rat carotid body. Acta Anat 126:226-229.
9. Beitner-Johnson D, Millhorn DE. 1998. Hypoxia induces phosphorylation of the cyclic AMP response element-binding protein by a novel signaling mechanism. J Biol Chem 273:19834-19839.
10. Bisgard GE. 1994. The role of arterial chemoreceptors in ventilatory acclimatization to hypoxia. Adv Exp Med Biol 360:109-122.
11. Bisgard GE. 2000. Carotid body mechanisms in acclimatization to hypoxia. Respir Physiol 121:237-246.
12. Bisgard GE, Forster HV. 1996. Ventilatory responses to acute and chronic hypoxia. In: Fregly MJ, Blatteis CM, editors. Handbook of Physiology, Section 4. Environmental Physiology. London: Oxford University Press. p 1207-1239.
13. Carpenter E, Bee D, Peers C. 1998. Ionic currents in carotid body type I cells isolated from normoxic and chronically hypoxic adult rats. Brain Res 811:79-87.
14. Chen J, Dinger B, Jyung R, Stensaas L, Fidone S. 1997. Up-regulation of vascular endothelial growth factor (VEGF) and VEGF receptor (FLK-1) in chronically hypoxic rat carotid body. Soc Neurosci Abst 23:433.
15. Chen J, Major J, Dinger B, Stensaas L, Fidone S. 1998. Inhibition of hypoxia-induced angiogenesis in the rat carotid body by a growth factor-receptor blocker. FASEB J 12:A168.
16. Chen J, He L, Dinger B, Fidone S. 2000a. Pharmacological effects of endothelin in rat carotid body. Activation of second messenger pathways and potentiation of chemoreceptor activity. Adv Exp Med Biol 475:517-525.
17. Chen J, He L, Dinger B, Fidone S. 2000b. Cellular mechanisms involved in rabbit carotid body excitation elicited by endothelin peptides. Respir Physiol 121:13-23.
18. Chen J, Dinger B, Stensaas L, Fidone S. 2001. Involvement of vascular endothelial growth factor (VEGF) in carotid body vascular remodeling induced by chronic hypoxia. FASEB J A153.
19. Claps A, Torrealba F. 1988. The carotid body connections: A WGA-HRP study in the cat. Brain Res 455:123-133.
20. Clarke JA, de Burgh Daly M, Ead HW. 1990. Comparison of the size of the vascular compartment of the carotid body of the fetal, neonatal and adult cat. Acta Anat 138:166-174.
21. Clarke JA, Daly MB, Marshall JM, Ead HW, Hennessy EM. 2000. Quantitative studies of the vasculature of the carotid body in the chronically hypoxic rat. Braz J Med Biol Res 33:331-340.
22. Czyzyk-Krzeska MF, Bayliss DA, Lawson EE, Millhorn DE. 1992. Regulation of tyrosine hydroxylase gene expression in the rat carotid body by hypoxia. J Neurochem 58:1538-1546.
23. De Castro F, Rubio M. 1968. The anatomy and innervation of the blood vessels of the carotid body and the role of chemoreceptive reactions in the autoregulation of the blood flow. In: Torrance RW, editor. Arterial Chemoreceptors. Oxford: Blackwell. p 267-277.
24. Delpiano MA, Acker H. 1991. Hypoxia increases the cyclic AMP content of the cat carotid body in vitro. J Neurochem 57:291-297.
25. Dhillon DP, Barer GR, Walsh M. 1984. The enlarged carotid body of the chronically hypoxic and chronically hypoxic and hypercapnic rat: A morphometric analysis. Q J Exp Physiol 69:301-317.
26. DiGiulio C, Grilli A, De Lutiis MA, Di Natale F, Sabatino G, Felaco M. 1998. Does chronic hypoxia increase rat carotid body nitric oxide? Comp Biochem Physiol 120:243-247.
27. Dinger B, He L, Chen J, Stensaas L, Fidone S. 2001. The effect of chronic hypoxia on purinergic synaptic transmission in rat carotid body. FASEB J A153.
28. Dwinell MR, Powell FL. 1999. Chronic hypoxia enhances the phrenic nerve response to arterial chemoreceptor stimulation in anesthetized rats. J Appl Physiol 87:817-823.
29. Edwards C, Heath D, Harris P, Castillo Y, Kruger H, Arias-Stella J. 1971. The carotid body in animals at high altitude. J Pathol 104: 231-238.
30. Erickson JT, Mayer C, Jawa A, Ling L, Olson EB, Vidruk EH, Mitchell GS, Katz DM. 1998. Chemoafferent degeneration and carotid body hypoplasia following chronic hyperoxia in newborn rats. J Physiol 509:519-526.
31. Eyzaguirre C. 2000. Carotid body gap junctions: Secretion of transmitters and possible electric coupling between glomus cells and nerve terminals. Adv Exp Med Biol 475:349-357.
32. Finley JC, Katz DM. 1992. The central organization of carotid body afferent projections to the brainstem of the rat. Brain Res 572:108-116.
33. Finley JCW, Polak J, Katz DM. 1992. Transmitter diversity in carotid body afferent neurons: Dopaminergic and peptidergic phenotypes. Neuroscience 572:108-116.
34. Fitzgerald RS, Shirahata M, Ide T. 1997. Further cholinergic aspects of carotid body chemotransduction of hypoxia in cats. J Appl Physiol 82:819-827.
35. Fuller DD, Wang ZY, Ling L, Olson EB, Bisgard GE, Mitchell GS. 2001. Induced recovery of hypoxic phrenic responses in adult rats exposed to hyperoxia for the first month of life. J Physiol 536:917-926.
36. Gauda EB, Shirahata M, Fitzgerald RS. 1994. D2-dopamine receptor mRNA in the carotid body and petrosal ganglia in the developing cat. Adv Exp Med Biol 360:317-319.
37. Gonzalez C, Almaraz L, Obeso A, Rigual R. 1994. Carotid body chemoreceptors: From natural stimuli to sensory discharges. Physiol Rev 74:829-898.
38. Gonzalez C, Lopez-Lopez JR, Obeso A, Perez-Garcia MT, Rocher A. 1995. Cellular mechanisms of oxygen chemoreception in the carotid body. Respir Physiol 102:137-147.
39. Grimes PA, Mokashi A, Stone RA, Lahiri S. 1995. Nitric oxide synthase in autonomic innervation of the cat carotid body. J Auton Nerv Syst 54:80-86.
40. Habeck JO, Kummer W. 1993. Neuronal and neuroendocrine markers in the human carotid body in health and disease. Adv Exp Med Biol 337:31-35.
41. Hanbauer I. 1977. Regulation of tyrosine hydroxylase in carotid body. Adv Biochem Psychopharmacol 16:275-280.
42. Hanbauer I, Karoum F, Hellstrom S, Lahiri S. 1981. Effects of hypoxia lasting up to one month on the catecholamine content in rat carotid body. Neuroscience 6:81-86.
43. He L, Chen J, Dinger B, Stensaas L, Fidone S. 1996. Endothelin modulates chemoreceptor cell function in mammalian carotid body. Adv Exp Med Biol 410:305-311.
44. Heath D, Smith P, Fitch R. 1985. Comparative pathology of the enlarged carotid body. J Comp Pathol 95:259-271.
45. Hellstrom S. 1975. Morphometric studies of dense-cored vesicles in type I cells of the rat carotid body. J Neurocytol 4:77-86.
46. Hess A. 1968. Electron microscopic observations of normal and experimental cat carotid bodies. In: Torrance RW, editor. Arterial chemoreceptors. Oxford: Blackwell. p 51-56.
47. Huey KA, Powell FL. 2000. Time-dependent changes in dopamine D(2)-receptor mRNA in the arterial chemoreflex pathway with chronic hypoxia. Mol Brain Res 75:264-270.
48. Huey KA, Brown IP, Jordan MC, Powell FL. 2000. Changes in dopamine D(2)-receptor modulation of the hypoxic ventilatory response with chronic hypoxia. Respir Physiol 123:177-187.
49. Ichikawa H, Rabchevsky A, Helke CJ. 1993. Presence and coexistence of putative neurotransmitters in carotid sinus baro- and chemoreceptor afferent neurons. Brain Res 611:67-74.
50. Jackson A, Nurse C. 1997. Dopaminergic properties of cultured rat carotid body chemoreceptors grown in normoxic and hypoxic environments. J Neurochem 69:645-654.
51. Jackson A, Nurse CA. 1998. Role of acetylcholine receptors and dopamine transporter in regulation of extracellular dopamine in rat carotid body cultures grown in chronic hypoxia or nicotine. J Neurochem. 70:653-662.
52. Kameda Y. 1996. Ultrastructural immunogold localization of vimentin and S-100 protein in guinea pig pars tuberalis. J Histochem Cytochem 44:511-518.
53. Kameda Y, Miura M, Hayashida Y. 1998. Different effects of prolonged isocapnic hypoxia on the carotid body and the glomus cells in the wall of the common carotid artery of the chicken. Brain Res 805:191-206.
54. Kirby GC, McQueen DS. 1984. Effects of antagonists MDL 72222 and ketanserin on response of cat carotid body chemoreceptors to 5-hydroxytryptamine. Br J Pharmacol 83:259-269.
55. Kondo H, Iwasa H. 1996. Re-examination of the carotid body ultrastructure with special attention to intercellular membrane appositions. Adv Exp Med Biol 410:45-50.
56. Kondo H, Iwanaga T, Nakajima T. 1982. Immunocytochemical study on the localization of neuron-specific enolase and S-100 protein in the carotid body of rats. Cell Tiss Res 227:291-295.
57. Kusakabe T, Hayashida Y, Matsuda H, Gono Y, Powell FL, Ellisman MH, Kawakami T, Takenaka T. 1998a. Hypoxic adaptation of the peptidergic innervation in the rat carotid body. Brain Res 806:165-174.
58. Kusakabe T, Matsuda H, Harada Y, Hayashida Y, Gono Y, Kawakami T, Takenaka T. 1998b. Changes in the distribution of nitric oxide synthase immunoreactive nerve fibers in the chronically hypoxic rat carotid body. Brain Res 795:292-296.
59. Lahiri S. 2000. Plasticity and multiplicity in the mechanisms of oxygen sensing. Adv Exp Med Biol 475:13-23.
60. Lahiri S, DeLaney RG, Brody JS, Simpser M, Velasquez T, Motoyama EK, Polgar C. 1976. Relative role of environmental and genetic factors in respiratory adaptation to high altitude. Nature 261:133-135.
61. Lahiri S, Smatresk N, Pokorski M, Barnard P, Mokashi A, McGregor KH. 1984. Dopaminergic efferent inhibition of carotid body chemoreceptors in chronically hypoxic cats. Am J Physiol 247:R24-28.
62. Lahiri S, Mulligan E, Andronikou S, Shirahata M, Mokashi A. 1987. Carotid body chemosensory function in prolonged normobaric hyperoxia in the cat. J Appl Physiol 62:1924-1931.
63. Lahiri S, Rozanov C, Cherniack NS. 2000. Altered structure and function of the carotid body at high altitude and associated chemoreflexes. High Altitude Med Biol 1:63-74.
64. Lahiri S, Rozanov C, Roy A, Storey B, Buerk DG. 2001. Regulation of oxygen sensing in peripheral arterial chemoreceptors. Int J Biochem Cell Biol 33:755-774.
65. Laidler P, Kay JM. 1975. A quantitative morphological study of the carotid bodies of rats living at a simulated altitude of 4300 metres. J Pathol 117:183-191.
66. Laidler P, Kay JM. 1978. A quantitative study of some ultrastructural features of the type I cells in the carotid bodies of rats living at a simulated altitude of 4300 metres. J Neurocytol 7:183-192.
67. Le Douarin N. 1982. The Neural Crest. London: Cambridge University Press.
68. McDonald DM. 1981. Peripheral chemoreceptors: Structure-function relationships of carotid body. In: Hornbein TF, Lenfant C, editors. Regulation of Breathing. New York: Marcel Decker. p 105-320.
69. McDonald DM. 1983a. Morphology of the rat carotid sinus nerve. I. Course, connections, dimensions and ultrastructure. J Neurocytol 12:345-372.
70. McDonald DM. 1983b. Morphology of the rat carotid sinus nerve. II. Number and size of axons. J Neurocytol 12:373-392.
71. McDonald DM, Haskell A. 1984. Morphology of connections between arteriols and capillaries in the rat carotid body analyzed by reconstructing serial sections. In: Pollot DJ, editor. The Peripheral Arterial Chemoreceptors. London: Croom Helm. p 195-206.
72. McDonald DM, Larue DT. 1983. The ultrastructure and connections of blood vessels supplying the rat carotid body and carotid sinus. J Neurocytol 12:117-153.
73. McDonald DM, Mitchell RA. 1975. The innervation of glomus cells, ganglion cells and blood vessels in the rat carotid body: A quantitative ultrastructural study. J Neurocytol 4:177-230.
74. McGregor KH, Gil J, Lahiri S. 1984. A morphometric study of the carotid body in chronically hypoxic rats. J Appl Physiol 57:1430-1438.
75. Millhorn DE, Raymond R, Conforti L, Zhu W, Beitner-Johnson D, Filisko T, Genter MB, Kobayashi S, Peng M. 1997. Regulation of gene expression for tyrosine hydroxylase in oxygen sensitive cells by hypoxia. Kidney Int 51:527-535.
76. Mills L, Nurse C. 1993. Chronic hypoxia in vitro increases volume of dissociated carotid body chemoreceptors. NeuroReport 4:619-622.
77. Mitchell GS, Baker TL, Nanda SA, Fuller DD, Zabka AG, Hodgeman BA, Bavis RW, Mack KJ, Olson EB Jr. 2001. Intermittent hypoxia and respiratory plasticity. J Appl Physiol 90:2466-2475.
78. Olson EB Jr, Vidruk EH, McCrimmon DR, Dempsey JA. 1983. Monoamine neurotransmitter metabolism during acclimatization to hypoxia in rats. Respir Physiol 54:79-96.
79. Pallot DJ. 1987. The mammalian carotid body. Adv Anat Embryol Cell Biol 102:1-91.
80. Pallot DJ, Al Neamy KW, Blakeman N. 1986. Quantitative studies of rat carotid body type I cells. Acta Anat 126:187-192.
81. Peers C, Carpenter E, Hatton CJ, Wyatt CN, Bee D. 1996. Ca2+ channel currents in type I carotid body cells of normoxic and chronically hypoxic neonatal rats. Brain Res 739:251-257.
82. Peng YJ, Kline DD, Hamedani A, Prabhakar NR. 2001a. Induction of long term facilitation in the carotid body activity by intermittent hypoxia. FASEB J 15:A153.
83. Peng YJ, Kline DD, Dick TE, Prabhakar NR. 2001b. Chronic intermittent hypoxia enhances carotid body chemoreceptor response to low oxygen. Adv Exp Med Biol 499:33-38.
84. Pequignot J-M, Hellstrom S, Johansson C. 1984. Intact and sympathectomized carotid bodies of long-term hypoxic rats: A morphometric ultrastructural study. J Neurocytol 13:481-493.
85. Pequignot JM, Cottet-Emard JM, Dalmaz Y, Peyrin L. 1987. Dopamine and norepinephrine dynamics in rat carotid body during long- term hypoxia. J Auton Nerv Sys 21:9-14.
86. Perez-Garcia MT, Almaraz L, Gonzalez C. 1990. Effects of different types of stimulation on cyclic AMP content in the rabbit carotid body: Functional significance. J Neurochem 55:1287-1293.
87. Pizarro J, Ryan ML, Hedrick MS, Xue DH, Keith IM, Bisgard GE. 1995. Intracarotid substance P infusion inhibits ventilation in the goat. Respir Physiol 101:11-22.
88. Powell FL, Garcia N. 2000. Physiological effects of intermittent hypoxia. High Altitude Med Biol 1:125-136.
89. Prabhakar NR. 1999. NO and CO as second messengers in oxygen sensing in the carotid body. Respir Physiol 115:161-168.
90. Prabhakar NR. 2000. Oxygen sensing by carotid body chemoreceptors. J Appl Physiol 88:2287-2295.
91. Prabhakar NR. 2001. Oxygen sensing during intermittent hypoxia: Cellular and molecular mechanisms. J Appl Physiol 90:1986-1994.
92. Prabhakar NR, Overholt JL. 2000. Cellular mechanisms of oxygen sensing at the carotid body: Heme proteins and ion channels. Respir Physiol 122:209-221.
93. Prabhakar NR, Runold M, Yamamoto Y, Lagercrantz H, von Euler C. 1984. Effect of substance P antagonist on the hypoxia-induced carotid chemoreceptor activity. Acta Physiol Scand 121:301-303.
94. Prabhakar NR, Landis SC, Kumar GK, Mullikin-Kilpatrick D, Cherniack NS, Leeman S. 1989. Substance P and neurokinin A in the cat carotid body: Localization, exogenous effects and changes in content in response to arterial pO2. Brain Res 481:205-214.
95. Prabhakar NR, Cao H, Lowe JA 3rd, Snider RM. 1993. Selective inhibition of the carotid body sensory response to hypoxia by the substance P receptor antagonist CP-96,345. Proc Natl Acad Sci USA 90:10041-10045.
96. Qu L, Stuesse SL. 1990. Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits. Peptides 11:955-961.
97. Scheibner T, Read DJ, Sullivan CE. 1988. Distribution of substance P-immunoreactive structures in the developing cat carotid body. Brain Res 453:72-78.
98. Shirahata M, Schofield B, Chin BY, Guilarte TR. 1994. Culturing carotid body cells of adult cats. Adv Exp Med Biol 360:163-165.
99. Smith P, Gosney J, Heath D, Burnett H. 1990. The occurrence and distribution of certain polypeptides within the human carotid body. Cell Tissue Res 261:565-571.
100. Tatsumi K, Pickett CK, Weil JV. 1995. Decreased carotid body sensitivity in chronic hypoxia: Role of dopamine. Respir Physiol 101:47-57.
101. Verna A. 1979. Ultrastructure of the carotid body in the mammals. Int Rev Cytol 60:271-330.
102. Verna A. 1997. The mammalian carotid body: Morphological data. In: Gonzalez C, editor. The Carotid Body Chemoreceptors. Austin, TX: Landes Bioscience. p 1-29.
103. Verna A, Barets A, Salat C. 1984. Distribution of sympathetic nerve endings within the rabbit carotid body: A histochemical and ultrastructural study. J Neurocytol 13:849-865.
104. Verna A, Schamel A, Pequignot JM. 1993. Long-term hypoxia increases the number of norepinephrine-containing glomus cells in the rat carotid body: A correlative immunocytochemical and biochemical study. J Auton Nerv System 44:171-177.
105. Verna A, Schamel A, Le Moine C, Bloch B. 1995. Localization of dopamine D2 receptor mRNA in glomus cells of the rabbit carotid body by in situ hybridization. J Neurocytol 24:265-270.
106. Wach RA, Bee D, Barer GR. 1989. Dopamine and ventilatory effects of hypoxia and almitrine in chronically hypoxic rats. J Appl Physiol 67:186-192.
107. Wang ZZ, Stensaas LJ, de Vente J, Dinger B, Fidone SJ. 1991. Immunocytochemical localization of cAMP and cGMP in cells of the rat carotid body following natural and pharmacological stimulation. Histochemistry 96:523-530.
108. Wang ZZ, Stensaas LJ, Dinger B, Fidone SJ. 1992. The co-existence of biogenic amines and neuropeptides in the type I cells of the cat carotid body. Neuroscience 47:473-480.
109. Wang ZZ, Bredt DS, Fidone SJ, Stensaas LJ. 1993. Neurons synthesizing nitric oxide innervate the mammalian carotid body. J Comp Neurol 336:419-432.
110. Wang ZZ, Dinger B, Fidone SJ, Stensaas LJ. 1998. Changes in tyrosine hydroxylase and substance P immunoreactivity in the cat carotid body following chronic hypoxia and denervation. Neuroscience 83:1273-1281.
111. Wang ZY, Baker TL, Keith IM, Mitchell GS, Bisgard GE. 2000a. Continuous, but not episodic hypoxia, induces CREB phosphorylation in rat carotid body type I cells. Adv Exp Med Biol 475:631-635.
112. Wang ZY, Keith IM, Beckman MJ, Brownfield MS, Vidruk EH, Bisgard GE. 2000b. 5-HT5a receptors in the carotid body chemoreception pathway of rat. Neurosci Lett 278:9-12.
113. 3 receptors in primary sensory neurons of the petrosal ganglion of adult rats. Auton Neurosci Basic Clin 95:121-124.
114. Wyatt CN, Wright C, Bee D, Peers C. 1995. O2-sensitive K+ currents in carotid body chemoreceptor cells from normoxic and chronically hypoxic rats and their roles in hypoxic chemotransduction. Proc Natl Acad Sci USA 92:295-299.
115. Zapata P. 1997. Chemosensory activity in the carotid nerve: effects of pharmacological agents. In: Gonzalez C, editor. The Carotid Body Chemoreceptors. Austin, TX: Landes Bioscience. p 119-146.
116. 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.