Mechanisms of disease: Acute oxygen-sensing mechanisms

New England Journal of Medicine

Volumn 353, Issue 19, 2005, Pages 2042-2055

  Weir, E Kenneth ^a,e   López Barneo, José ^b   Buckler, Keith J ^c   Archer, Stephen L ^d  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF SEVILLE   (Spain)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d UNIVERSITY OF ALBERTA   (Canada)

^e VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANOREXIGENIC AGENT; CALCIUM CHANNEL BLOCKING AGENT; DEXFENFLURAMINE; DICHLOROACETIC ACID; DOPAMINE; ENDOTHELIN; INDOMETACIN; NIFEDIPINE; NITRIC ACID; OXYGEN; PRASTERONE; PROSTACYCLIN; PROSTAGLANDIN SYNTHASE INHIBITOR; RHO KINASE INHIBITOR; SILDENAFIL; THROMBOXANE A2; VASOCONSTRICTOR AGENT; VASODILATOR AGENT; POTASSIUM CHANNEL;

CALCIUM TRANSPORT; CAROTID BODY; DYSPNEA; HUMAN; LUNG ARTERY; LUNG VASOCONSTRICTION; NONHUMAN; OXYGEN SENSING; OXYGEN TENSION; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVIEW; SARCOPLASMIC RETICULUM; SMOOTH MUSCLE FIBER MEMBRANE; VASCULAR RESISTANCE; ANOXIA; CELL HYPOXIA; HOMEOSTASIS; LUNG EDEMA; METABOLISM; OXIDATION REDUCTION REACTION; PATENT DUCTUS ARTERIOSUS; PATHOPHYSIOLOGY; PHYSIOLOGY; VASOCONSTRICTION;

ANOXIA; CELL HYPOXIA; DUCTUS ARTERIOSUS, PATENT; HOMEOSTASIS; HUMANS; HYPERTENSION, PULMONARY; OXIDATION-REDUCTION; OXYGEN; POTASSIUM CHANNELS; PULMONARY EDEMA; VASOCONSTRICTION;

EID: 27744529463     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra050002     Document Type: Review

References (115)

1. Priestly J. Experiments and observations on different kinds of air. 2nd ed. London: J. Johnson, 1775:101.
2. Hales CA, Westphal D. Hypoxemia following the administration of sublingual nitroglycerin. Am J Med 1978;65:911-8.
3. Motley H, Cournard A, Werko L, Himmelstein A, Dresdale D. The influence of short periods of induced acute anoxia upon pulmonary artery pressures in man. Am J Physiol 1947;150:315-20.
4. Hambraeus-Jonzon K, Bindslev L, Mellgard A, Hedenstierna G. Hypoxic pulmonary vasoconstriction in human lungs: a stimulus-response study. Anesthesiology 1997;86:308-15.
5. Dorrington KL, Clar C, Young JD, Jonas M, Tansley JG, Robbins PA. Time course of the human pulmonary vascular response to 8 hours of isocapnic hypoxia. Am J Physiol 1997;273:H1126-H1134.
6. Madden JA, Vadula MS, Kurup VP. Effects of hypoxia and other vasoactive agents on pulmonary and cerebral artery smooth muscle cells. Am J Physiol 1992;263:L384-L393.
7. Post JM, Hume JR, Archer SL, Weir EK. Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol 1992;262:C882-C890.
8. Yuan X-J, Goldman WF, Tod ML, Rubin LJ, Blaustein MP. Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. Am J Physiol 1993;264:L116-L123.
9. +]i to hypoxia in pulmonary arterial smooth muscle. Am J Physiol Lung Cell Mol Physiol 2002;283:L1143-L1150.
10. Archer SL, Huang JM, Reeve HL, et al. The differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia. Circ Res 1996;78:431-42.
11. Michelakis ED, Thebaud B, Weir EK, Archer SL. Hypoxic pulmonary vasoconstriction: redox regulation of O(2)-sensitive K(+) channels by a mitochondrial O(2)-sensor in resistance artery smooth muscle cells. J Mol Cell Cardiol 2004;37:1119-36.
12. Cornfield DN, Reeve HL, Tolarova S, Weir EK, Archer S. Oxygen causes fetal pulmonary vasodilation through activation of a calcium-dependent potassium channel. Proc Natl Acad Sci U S A 1996;93:8089-94.
13. Archer SL, Wu XC, Thebaud B, et al. Preferential expression and function of voltage-gated, O2-sensitive K+ channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells. Circ Res 2004;95:308-18.
14. McMurtry IF, Petrun MD, Reeves JT. Lungs from chronically hypoxic rats have decreased pressor response to acute hypoxia. Am J Physiol 1978;235:H104-H109.
15. Smirnov SV, Robertson TP, Ward JP, Aaronson PI. Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells. Am J Physiol 1994;266:H365-H370.
16. Osipenko ON, Alexander D, MacLean MR, Gurney AM. Influence of chronic hypoxia on the contributions of non-inactivating and delayed rectifier K currents to the resting potential and tone of rat pulmonary artery smooth muscle. Br J Pharmacol 1998;124:1335-7.
17. Krick S, Platoshyn O, McDaniel SS, Rubin LJ, Yuan JX. Augmented K(+) currents and mitochondrial membrane depolarization in pulmonary artery myocyte apoptosis. Am J Physiol Lung Cell Mol Physiol 2001;281:L887-L894.
18. Reeve HL, Michelakis E, Nelson DP, Weir EK, Archer SL. Alterations in a redox oxygen sensing mechanism in chronic hypoxia. J Appl Physiol 2001;90:2249-56.
19. Pozeg ZI, Michelakis ED, McMurtry MS, et al. In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 2003;107:2037-44.
20. Osipenko ON, Tate RJ, Gurney AM. Potential role for Kv3.1b channels as oxygen sensors. Circ Res 2000;86:534-40.
21. Hogg DS, Davies AR, McMurray G, Kozlowski RZ. K(V)2.1 channels mediate hypoxic inhibition of I(KV) in native pulmonary arterial smooth muscle cells of the rat. Cardiovasc Res 2002;55:349-60.
22. Robertson TP, Hague D, Aaronson PI, Ward JP. Voltage-independent calcium entry in hypoxic pulmonary vasoconstriction of intrapulmonary arteries of the rat. J Physiol 2000;525:669-80.
23. Burghuber OC. Nifedipine attenuates acute hypoxic pulmonary vasoconstriction in patients with chronic obstructive pulmonary disease. Respiration 1987;52:86-93.
24. Salvaterra CG, Goldman WF. Acute hypoxia increases cytosolic calcium in cultured pulmonary arterial myocytes. Am J Physiol 1993;264:L323-L328.
25. Dipp M, Nye PC, Evans AM. Hypoxic release of calcium from the sarcoplasmic reticulum of pulmonary artery smooth muscle. Am J Physiol Lung Cell Mol Physiol 2001;281:L318-L325.
26. Morio Y, McMurtry IF. Ca2+ release from ryanodine-sensitive store contributes to mechanism of hypoxic vasoconstriction in rat lungs. J Appl Physiol 2002;92:527-34.
27. 2+ entry. Am J Physiol Lung Cell Mol Physiol 2005;288:L1059-L1069.
28. 2+ and nonselective cation channel antagonists. Am J Physiol Lung Cell Mol Physiol 2005;289:L5-L13.
29. 2+ entry in isolated canine pulmonary arterial smooth muscle cells. J Physiol 2005;563:409-19.
30. Landsberg JW, Yuan J-X. Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol Sci 2004;19:44-50.
31. Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and non-muscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 2003;83:1325-58.
32. Robertson TP, Aaronson PI, Ward JP. Hypoxic vasoconstriction and intracellular Ca2+ in pulmonary arteries: evidence for PKC-independent Ca2+ sensitization. Am J Physiol 1995;268:H301-H307.
33. Wang Z. Jin N, Ganguli S, Swartz DR, Li L, Rhoades RA. Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction. Am J Respir Cell Mol Biol 2001;25:628-35.
34. Ward JP, Knock GA, Snetkov VA, Aaronson PI. Protein kinases in vascular smooth muscle tone - role in the pulmonary vasculature and hypoxic pulmonary vasoconstriction. Pharmacol Ther 2004;104:207-31.
35. Robertson TP, Dipp M, Ward JP, Aaronson PI, Evans AM. Inhibition of sustained hypoxic vasoconstriction by Y-27632 in isolated intrapulmonary arteries and perfused lung of the rat. Br J Pharmacol 2000;131:5-9.
36. Fagan KA, Oka M, Bauer NR, et al. Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension in mice by inhibition of Rho-kinase. Am J Physiol Lung Cell Mol Physiol 2004;287:L656-L664.
37. Alzamora-Castro V, Battilana G, Abigattas R, Sialer S. Patent ductus arteriosus and high altitude. Am J Cardiol 1960;5:761-3.
38. Tristani-Firouzi M, Reeve HL, Tolarova S, Weir EK, Archer SL. Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel. J Clin Invest 1996;98:1959-65.
39. Michelakis ED, Rebeyka I, Wu X, et al. O2 sensing in the human ductus arteriosus: regulation of voltage-gated K+ channels in smooth muscle cells by a mitochondrial redox sensor. Circ Res 2002;91:478-86.
40. Michelakis E, Rebeyka I, Bateson J, Olley P, Puttagunta L, Archer S. Voltage-gated potassium channels in human ductus arteriosus. Lancet 2000;356:134-7.
41. 2 in type I chemoreceptor cells. Science 1988;241:580-2.
42. Ganfornina MD, Lopez-Barneo J. Potassium channel types in arterial chemoreceptor cells and their selective modulation by oxygen. J Gen Physiol 1992;100:401-26.
43. 2-sensitive K+ currents in carotid body chemoreceptor cells from normoxic and chronically hypoxic rats and their role in hypoxic chemotransduction. Proc Natl Acad Sci U S A 1995;92:295-9.
44. Buckler KJ. A novel oxygen-sensitive potassium current in rat carotid body type I cells. J Physiol 1997;498:649-62.
45. Buckler KJ, Williams BA, Honore E. An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells. J Physiol 2000;525:135-42.
46. Buckler KJ, Vaughan-Jones RD. Effects of hypoxia on membrane potential and intracellular calcium in rat neonatal carotid body type I cells. J Physiol 1994;476:423-8.
47. Urena J, Fernadez-Chacon R, Benot AR, Alvarez de Toledo GA, Lopez-Barneo J. Hypoxia induces voltage-dependent Ca2+ entry and quantal dopamine secretion in carotid body glomus cells. Proc Natl Acad Sci U S A 1994;91:10208-11.
48. Montoro RJ, Urena J, Fernandez-Chacon R, Alvarez de Toledo G, Lopez-Barneo J. Oxygen sensing by ion channels and chemotransduction in single glomus cells. J Gen Physiol 1996;107:133-43.
49. Pardal R, Ludewig U, Garcia-Hirschfeld J, Lopez-Barneo J. Secretory responses of intact glomus cells in thin slices of rat carotid body to hypoxia and tetraethylammonium. Proc Natl Acad Sci U S A 2000;97:2361-6.
50. Peers C. Effects of doxapram on ionic currents recorded in isolated type I cells of the neonatal rat carotid body. Brain Res 1991;568:116-22.
51. Severinghaus JW, Bainton CR, Carcelen A. Respiratory insensitivity to hypoxia in chronically hypoxic man. Respir Physiol 1966;1:308-34.
52. Shimoda LA, Manalo DJ, Sham JS, Semenza GL, Sylvester JT. Partial HIF-1alpha deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia. Am J Physiol Lung Cell Mol Physiol 2001;281:L202-L208.
53. Howard RB, Hosokawa T, Maguire HH. Hypoxia-induced fetoplacental vasoconstriction in perfused human placental cotyledons. Am J Obstet Gynecol 1987;157:1261-6.
54. Hampl V, Bibova J, Stranek Z, et al. Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition. Am J Physiol Heart Circ Physiol 2002;283:H2440-H2449.
55. Lauweryns JM, Cokelaere M, Deleersynder M, Liebens M. Intrapulmonary neuroepithelial bodies in newborn rabbits: influence of hypoxia, hyperoxia, hypercapnia, nicotine, reserpine, L-DOPA and 5-HTP. Cell Tissue Res 1977;182:425-40.
56. Kemp PJ, Lewis A, Hartness ME, et al. Airway chemotransduction: from oxygen sensor to cellular effector. Am J Respir Crit Care Med 2002;166:S17-S24.
57. Fu XW, Nurse CA, Wong V, Cutz E. Hypoxia-induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit. J Physiol 2002;539:503-10.
58. Youngson C, Nurse C, Yeger H, Cutz E. Oxygen sensing in airway chemoreceptors. Nature 1993;365:153-5.
59. O'Kelly I, Lewis A, Peers C, Kemp PJ. O(2) sensing by airway chemoreceptorderived cells: protein kinase C activation reveals functional evidence for involvement of NADPH oxidase. J Biol Chem 2000;275:7684-92.
60. Zhu WH, Conforti L, Czyzyk-Krzeska MF, Milhorn DE. Membrane depolarization in PC-12 cells during hypoxia is regulated by an O2-sensitive K+ current. Am J Physiol 1996;271:C658-C665.
61. Jiang C, Haddad GG. Oxygen deprivation inhibits a K+ channel independently of cytosolic factors in rat central neurons. J Physiol 1994;481:15-26.
62. Jovanovic S, Crawford RM, Ranki HJ, Jovanovic A. Large conductance Ca2+-activated K+ channels sense acute changes in oxygen tension in alveolar epithelial cells. Am J Respir Cell Mol Biol 2003;28:363-72.
63. Conforti L, Petrovic M, Mohammad D, et al. Hypoxia regulates expression and activity of Kv1.3 channels in T lymphocytes: a possible role in T cell proliferation. J Immunol 2003;170:695-702.
64. Lopez-Barneo J, Pardal R, Ortega-Saenz P. Cellular mechanism of oxygen sensing. Annu Rev Physiol 2001;63:259-87.
65. Olschewski A, Hong Z, Peterson DA, Nelson DP, Porter VA, Weir EK. Opposite effects of redox status on membrane potential, cytosolic calcium, and tone in pulmonary arteries and ductus arteriosus. Am J Physiol Lung Cell Mol Physiol 2004;286:L15-L22.
66. Reeve H, Tolarova S, Nelson DP, Archer S, Weir EK. Redox control of oxygen sensing in the rabbit ductus arteriosus. J Physiol 2001;533:253-61.
67. Waypa GB, Schumacker PT. Hypoxic pulmonary vasoconstriction: redox events in oxygen sensing. J Appl Physiol 2005;98:404-14.
68. Fu XW, Wang D, Nurse CA, Dinauer MC, Cutz E. NADPH oxidase is an O2 sensor in airway chemoreceptors: evidence from K+ current modulation in wild-type and oxidase-deficient mice. Proc Natl Acad Sci U S A 2000;97:4374-9.
69. Archer SL, Reeve HL, Michelakis E, et al. O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Proc Natl Acad Sci U S A 1999;96:7944-9.
70. Roy A, Rozanov C, Mokashi A, et al. Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell [Ca(2+)](i) and respiratory responses to hypoxia. Brain Res 2000;872:188-93.
71. Wang D, Youngson C, Wong V, et al. NADPH-oxidase and a hydrogen peroxidesensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines. Proc Natl Acad Sci U S A 1996;93:13182-7.
72. Zulueta JJ, Yu FS, Hertig IA, Thannickal VJ, Hassoun PM. Release of hydrogen peroxide in response to hypoxia-reoxygenation: role of an NAD(P)H oxidase-like enzyme in endothelial cell plasma membrane. Am J Respir Cell Mol Biol 1995;12:41-9.
73. Waypa GB, Chandel NS, Schumacker PT. Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res 2001;88:1259-66.
74. Archer SL, Huang J, Henry T, Peterson D, Weir EK. A redox-based O2 sensor in rat pulmonary vasculature. Circ Res 1993;73:1100-12.
75. Archer SL, Wu XC, Thebaud B, Moudgil R, Hashimoto K, Michelakis ED. O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide. Biol Chem 2004;385:205-16.
76. Michelakis ED, Hampl V, Nsair A, et al. Diversity in mitochondrial function explains differences in vascular oxygen sensing. Circ Res 2002;90:1307-15.
77. Anichcov SV, Belen'kii ML. Pharmacology of the carotid body chemoreceptors. Crawford R, trans. New York: Macmillan, 1963.
78. Wyatt CN, Buckler KJ. The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol 2004;556:175-91.
79. Williams BA, Buckler KJ. Biophysical properties and metabolic regulation of a TASK-like potassium channel in rat carotid body type 1 cells. Am J Physiol Lung Cell Mol Physiol 2004;286:L221-L230.
80. Ortega-Saenz P, Pardal R, Garcia-Fernandez M, Lopez-Barneo J. Rotenone selectively occludes sensitivity to hypoxia in rat carotid body glomus cells. J Physiol 2003;548:789-800.
81. Williams SE, Wootton P, Mason HS, et al. Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science 2004;306:2093-7.
82. Tipparaju SM, Saxena N, Liu SQ, Kumar R, Bhatnagar A. Differential regulation of voltage-gated K+ channels by oxidized and reduced pyridine nucleotide coenzymes. Am J Physiol Cell Physiol 2005;288:C366-C376.
83. Chander A, Dhariwal KR, Viswanathan R, Venkitasubramanian TA. Pyridine nucleotides in lung and liver of hypoxic rats. Life Sci 1980;26:1935-45.
84. Leach RM, Hill HM, Snetkov VA, Robertson TP, Ward JP. Divergent roles of glycolysis and the mitochondrial electron transport chain in hypoxic pulmonary vasoconstriction of the rat: identity of the hypoxic sensor. J Physiol 2001;536:211-24.
85. Kaplin AI, Snyder SH, Linden DJ. Reduced nicotinamide adenine dinucleotideselective stimulation of inositol 1,4,5-trisphosphate receptors mediates hypoxic mobilization of calcium. J Neurosci 1996;16:2002-11.
86. Cherednichenko G, Zima AV, Feng W, Schaefer S, Blatter LA, Pessah IN. NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium-induced calcium release. Circ Res 2004;94:478-86.
87. Wilson HL, Dipp M, Thomas JM, Lad C, Galione A, Evans AM. ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase act as a redox sensor: a primary role for cyclic ADPribose in hypoxic pulmonary vasoconstriction. J Biol Chem 2001;276:11180-8.
88. Dipp M, Evans AM. Cyclic ADP-ribose is the primary trigger for hypoxic pulmonary vasoconstriction in the rat lung in situ. Circ Res 2001;89:77-83.
89. Yuan JX, Aldinger AM, Juhaszova M, et al. Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 1998;98:1400-6.
90. v channel expression and function in human pulmonary artery smooth muscle cells. Proc Am Thorac Soc 2005;2:A723. abstract.
91. Hughes FM Jr, Bortner CD, Purdy GD, Cidlowski JA. Intracellular K+ suppresses the activation of apoptosis in lymphocytes. J Biol Chem 1997;272:30567-76.
92. Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996;335:609-16.
93. Weir EK, Reeve HL, Huang JM, et al. Anorexic agents aminorex, fenfluramine, and dexfenfluramine inhibit potassium current in rat pulmonary vascular smooth muscle and cause pulmonary vasoconstriction. Circulation 1996;94:2216-20.
94. Hong Z, Olschewski A, Reeve HL, Nelson DP, Hong F, Weir EK. Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine. Am J Physiol Lung Cell Mol Physiol 2004;286:L531-L538.
95. Michelakis ED, Tymchak W, Noga M, et al. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation 2003;108:2066-9.
96. McMurtry M, Bonnet S, Wu X, et al. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 2004;95:830-40.
97. Peng W, Hoidal JR, Farrukh IS. Role of a novel KCa opener in regulating K+ channels of hypoxic human pulmonary vascular cells. Am J Respir Cell Mol Biol 1999;20:737-45.
98. Yu Y, Fantozzi I, Remillard CV, et al. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci U S A 2004;101:13861-6.
99. Curtis TM, Scholfield CN. Nifedipine blocks Ca2+ store refilling through a pathway not involving L-type Ca2+ channels in rabbit arteriolar smooth muscle. J Physiol 2001;532:609-23.
100. Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for longterm reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 1987;76:135-41.
101. Abe K, Shimokawa H, Morikawa K, et al. Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res 2004;94:385-93.
102. Nagaoka T, Fagan KA, Gebb SA, et al. Inhaled Rho kinase inhibitors are potent and selective vasodilators in rat pulmonary hypertension. Am J Respir Crit Care Med 2005;171:494-9.
103. Michelakis ED, Weir EK, Wu X, et al. Potassium channels regulate tone in rat pulmonary veins. Am J Physiol Lung Cell Mol Physiol 2001;280:L1138-L1147.
104. Maggiorini M, Melot C, Pierre S, et al. High-altitude pulmonary edema is initially caused by an increase in capillary pressure. Circulation 2001;103:2078-83.
105. Bartsch P, Mairbaurl H, Swenson ER, Maggiorini M. High altitude pulmonary oedema. Swiss Med Wkly 2003;133:377-84.
106. Ghofrani HA, Reichenberger F, Kohstall MG, et al. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med 2004;141:169-77.
107. Casalaz D. Ibuprofen versus indomethacin for closure of patent ductus arteriosus. N Engl J Med 2001;344:457-8.
108. Donnelly DF. Developmental aspects of oxygen sensing by the carotid body. J Appl Physiol 2000;88:2296-301.
109. Sullivan CE. Bilateral carotid body resection in asthma: vulnerability to hypoxic death in sleep. Chest 1980;78:354.
110. Timmers HJ, Wieling W, Karemaker MJ, Lenders JW. Denervation of carotid baroand chemoreceptors in humans. J Physiol 2003;553:3-11.
111. Gauda EB, McLemore GL, Tolosa J, Marston-Nelson J, Kwak D. Maturation of peripheral arterial chemoreceptors in relation to neonatal apnoea. Semin Neonatol 2004;9:181-94.
112. Perrin DG, Cutz E, Becker LE, Bryan AC, Madapallimatum A, Sole MJ. Sudden infant death syndrome: increased carotidbody dopamine and noradrenaline content. Lancet 1984;2:535-7.
113. Benot AR, Lopez-Barneo J. Feedback inhibition of Ca2+ currents by dopamine in glomus cells of the carotid body. Eur J Neurosci 1990;2:809-12.
114. Baysal BE, Myers EN. Etiopathogenesis and clinical presentation of carotid body tumors. Microsc Res Tech 2002;59:256-61.
115. Piruat JI, Pintado CO, Ortega-Saenz P, Roche M, Lopez-Barneo J. The mitochondrial SDHD gene is required for early embryogenesis and its partial deficiency results in persistent carotid body glomus cells activation with full responsiveness to hypoxia. Mol Cell Biol 2004;24:10933-40.