Similarities between the Oxygen Sensors of the Carotid Body and the Pulmonary Vascular Bed

  • S. Archer
  • E. K. Weir
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1995)


Aerobic organisms, including man, usually live within a fairly narrow range of oxygen tensions. The partial pressure of oxygen, PO2, in the arterial circulation of normal individuals ranges from near 100 mm Hg, at sea level, to approximately 40 mm Hg in normal individuals at an altitude equivalent to the summit of Everest [1]. Survival at higher or lower PO2 levels is not possible for more than brief periods. To achieve such tight control of oxygenation, man, and most aerobic organisms, is equipped with chemoreceptors which sense the oxygen level in the arteries or alveoli and, if hypoxia is detected, elicit a coordinated, multi-system response which attempts to correct hypoxemia or alveolar hypoxia. In humans, there are central chemoreceptors in the brain and peripheral chemoreceptors in the arterial vasculature (the carotid and aortic bodies). The carotid body monitors arterial oxygenation and increases its rate of sinus nerve discharge progressively as arterial PO2 is reduced from 150–50 mm Hg [2]. It is responsible for virtually all of the increase in ventilation which occurs with hypoxemia in man, as demonstrated by the observation that patients lose hypoxic ventilatory drive following bilateral resection of the carotid bodies [3]. The afferent signal from the carotid body is relayed to the brainstem by cranial nerve IX and stimulates the respiratory center in the brainstem, resulting in an increased volume and rate of respiration which optimizes arterial oxygen content.


Pulmonary Artery NADPH Oxidase Carotid Body Oxygen Sensor Mitochondrial Electron Transport Chain 
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  1. 1.
    Groves BM, Reeves JT, Sutton JR, et al (1987) Operation Everest II: Elevated high-altitude pulmonary resistance unresponsive to oxygen. J Appl Physiol 63: 521–530PubMedGoogle Scholar
  2. 2.
    Mills E, Jobsis FF (1972) Mitochondrial respiratory chain of carotid body and chemoreceptor response to changes in oxygen tension. J Neurophysiol 35: 405–428PubMedGoogle Scholar
  3. 3.
    West J (1991) Control of Ventilation. In: West J (ed) Physiological Basis of Medical Practice. Williams & Wilkins, Baltimore, MD., pp 579–603Google Scholar
  4. 4.
    Harris P, Heath D (1986) Chemoreceptors and the pulmonary circulation. In: Harris P, Heath D (eds) The human pulmonary circulation. 3rd. Churchill Livingstone, New York, NY, pp 484–492Google Scholar
  5. 5.
    Arias-Stellas J, Valcarcel J (1973) The human carotid body at high altitudes. Pathol Microbiol 39: 292–299Google Scholar
  6. 6.
    Lopez-Barneo J, Lopez-Lopez J, Urena J, Gonzalez C (1988) Chemotransduction in the carotid body: K+ current modulated by PO2 in type 1 chemoreceptor cells. Science 241: 580–582PubMedCrossRefGoogle Scholar
  7. 7.
    Lopez-Barneo J, Benot A, Urena J (1993) Oxygen sensing and the electrophysiology of arterial chemoreceptor cells. NIPS 8: 191–195Google Scholar
  8. 8.
    Biscoe T, Duchen M (1990) Responses of type 1 cells dissociated from the rabbit carotid body to hypoxia. J Physiol London 428: 39–59PubMedGoogle Scholar
  9. 9.
    Salvaterra C, Goldman W (1993) Acute hypoxia increases cytosolic calcium in cultured pulmonary arterial myocytes. Lung Cell Mol Physiol 264: L323–L328Google Scholar
  10. 10.
    Buckler K, Vaughan-Jones R (1994) Effects of hypoxia on membrane potential and intracellular calcium in rat neonatal carotid body type 1 cells. J Physiol 476: 423–428PubMedGoogle Scholar
  11. 11.
    Ruppersberg J, Stocker M, Pongs O, Heinemann S, Frank R, Koenen M (1991) Regulation of fast inactivation of cloned mammalian 1K(A) channels by cysteine oxidation. Nature 352: 711–714PubMedCrossRefGoogle Scholar
  12. 12.
    Kuo S, Saad A, Koong A, Hahn G, Giaccia A (1993) Potassium-channel activation in response to low doses of g-irradiation involves reactive oxygen intermediates in nonexcitatory cells. Proc Natl Acad Sci 90: 908–912PubMedCrossRefGoogle Scholar
  13. 13.
    Post J, Weir E, Archer S, Hume J (1993) Redox regulation of K+ channels and hypoxic pulmonary vasoconstriction. In: Weir EK, Hume JR, Reeves JT (eds) Ion Flux in Pulmonary Vascular Control, Plenum Press, New York, pp 189–204CrossRefGoogle Scholar
  14. 14.
    Lee S, Park M, So I, Earm Y (1994) NADH and NAD modulates Ca2+-activated K + channels in small pulmonary arterial smooth muscle cells of the rabbit. Pflugers Arch 427: 378–380PubMedCrossRefGoogle Scholar
  15. 15.
    Yuan XJ, Goldman W, Tod M, Rubin L, Blaustein M (1993) Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. Am J Physiol 264: L116–L123PubMedGoogle Scholar
  16. 16.
    Yuan XJ, Tod M, Rubin L, Blaustein M (1994) Deoxyglucose and reduced glutathione mimic effects of hypoxia on K+ and Ca2+ conductances in pulmonary artery cells. Am J Physiol 267: L52–L63PubMedGoogle Scholar
  17. 17.
    Mulligan E, Lahiri S, Storey BT (1981) Carotid body O2 chemoreception and mitochondrial oxidative phosphorylation. J Appl Physiol 51: 438–446PubMedGoogle Scholar
  18. 18.
    Freeman B, Crapo J (1981) Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. J Biol Chem 256: 10986–10992PubMedGoogle Scholar
  19. 19.
    Archer S, Nelson D, Weir E (1989) Simultaneous measurement of oxygen radicals and pulmonary vascular reactivity in the isolated rat lung. J Appl Physiol 67: 1903–1911PubMedGoogle Scholar
  20. 20.
    Duchen M, Biscoe T (1992) Mitochondrial function in type 1 cells isolated from rabbit arterial chemoreceptors. J Physiol 450: 13–31PubMedGoogle Scholar
  21. 21.
    Roumy M, Leitner LM (1977) Role of Ca + + ions in the mechanism of arterial chemore- ceptor excitation. In: Acker H, Fidone S, Palloti D, et al (eds) Chemoreception in the carotid body, Springer, Berlin, pp 257–263CrossRefGoogle Scholar
  22. 22.
    Archer S, Huang J, Henry T, Peterson D, Weir E (1993) A redox-based O2 sensor in rat pulmonary vasculature. Circ Res 73: 1100–1112PubMedGoogle Scholar
  23. 23.
    Obeso A, Almaraz L, Gonzalez C (1988) Effects of cyanide and uncouplers on chemoreceptor activity and ATP content of the cat carotid body. Brain Res 481: 250–257CrossRefGoogle Scholar
  24. 24.
    Lahiri S (1994) Chromophores in O2 chemoreception: The carotid body model. NIPS 9: 161–165Google Scholar
  25. 25.
    Archer S, Will J, Weir E (1986) Redox status in the control of pulmonary vascular tone. Herz 11: 127–141PubMedGoogle Scholar
  26. 26.
    Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. Biochem J 134: 707–716PubMedGoogle Scholar
  27. 27.
    Archer S, Huang J, Post J, Hume J, Weir E (1993) t-butyl hydroperoxide and glutathione modulate an outward K + current in rat pulmonary vascular smooth muscle cells. Circulation 88: 1–143 (Abst)Google Scholar
  28. 28.
    Cross A, Henderson L, Jones O, Delpiano M, Hentschel J, Acker H (1990) Involvement of an NAD(P)H oxidase as a pO2 sensor protein in the rat carotid body. Biochem J 272: 743–747PubMedGoogle Scholar
  29. 29.
    Acker H, Dufau E, Huber J, Sylvester D (1989) Indications to an NADPH oxidase as a possible pO2 sensor in the rat carotid body. FEBS (Lett) 256: 75–78CrossRefGoogle Scholar
  30. 30.
    Gatley JS, Sheratt HSA (1976) Relation of binding of diphenylene[125I] iodonium to mitochondria to the extent of inhibition of oxygen uptake. Biochem J 158: 307–315PubMedGoogle Scholar
  31. 31.
    Lahiri S, Rumsey WL, Wilson DF, Iturriaga R (1993) Contribution of in vivo microvascular PO2 in the cat carotid body chemotransduction. J Appl Physiol 75: 1035–1043PubMedGoogle Scholar
  32. 32.
    Kato M, Staub N (1966) Response of small pulmonary arteries to unilobar alveolar hypoxia and hypercapnia. Circ Res 19: 426–440PubMedGoogle Scholar
  33. 33.
    Shirai M, Ninomiya I, Sada K (1991) Constrictor response of small pulmonary arteries to acute pulmonary hypertension during left atrial pressure elevation. Jap J Physiol 41: 129–142CrossRefGoogle Scholar
  34. 34.
    Bradford J, Dean H (1894) The pulmonary circulation. J Physiol 16: 34–96PubMedGoogle Scholar
  35. 35.
    von Euler U, Liljestrand G (1946) Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 12: 301–320CrossRefGoogle Scholar
  36. 36.
    Lloyd TC (1965) Pulmonary vasoconstriction during histotoxic hypoxia. J Appl Physiol 20: 488–490PubMedGoogle Scholar
  37. 37.
    Hampl V, Weir EK, Archer SL (1994) Endothelium-derived nitric oxide is less important for basal tone regulation in the pulmonary than the renal circulation of the adult rat. J Vasc Med Biol 5: 22–30Google Scholar
  38. 38.
    Susic D, Haxhiu M, Kentera D (1981) Decreased pulmonary pressor response to acute hypoxia in chronically hypoxic rats. Respiration 41: 166–173PubMedGoogle Scholar
  39. 39.
    Isaacson T, Hampl V, Weir E, Nelson D, Archer S (1994) Increased endothelium-derived nitric oxide in hypertensive pulmonary circulation of chronically hypoxic rats. J Appl Physiol 76: 933–940PubMedGoogle Scholar
  40. 40.
    Archer S, Weir E (1989) Mechanisms in hypoxic pulmonary hypertension. In: Wagenvoort C, Denolin H (eds) Pulmonary Circulation: Advances and Controversies. Elsevier, New York, pp 87–107Google Scholar
  41. 41.
    McMurtry I, Davidson B, Reeves J, Grover R (1976) Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res 38: 99–104PubMedGoogle Scholar
  42. 42.
    Harder D, Madden J, Dawson C (1985) Hypoxic induction of Ca2+-dependent action potentials in small pulmonary arteries of the cat. J Appl Physiol 59: 1389–1393PubMedGoogle Scholar
  43. 43.
    Madden J, Vadula M, Kurup V (1992) Effects of hypoxia and other vasoactive agents on pulmonary and cerebral artery smooth muscle cells. Am J Physiol 263: L384–L393PubMedGoogle Scholar
  44. 44.
    Cornfield D, Stevens T, McMurtry I, Abman S, Rodman D (1993) Acute hypoxia increases cytosolic calcium in fetal pulmonary artery smooth muscle cells. Am J Physiol 265: L1–L4Google Scholar
  45. 45.
    Marshall C, Cooper DY, Marshall BE (1988) Reduced availability of energy initiates pulmonary vasoconstriction. Proc Soc Exp Biol 187: 282–286PubMedGoogle Scholar
  46. 46.
    Lloyd TC (1966) PO2-dependent pulmonary vasoconstriction caused by procaine. J Appl Physiol 21: 1439–1442PubMedGoogle Scholar
  47. 47.
    Hottenstein O, Mitzner W, Bierkamper G (1982) Hypoxia alters membrane potential in the rat main pulmonary artery smooth muscle: A possible calcium mechanism. Physiologist 24: 276 (Abst)Google Scholar
  48. 48.
    McMurtry I (1985) Bay K8644 potentiates and A23187 inhibits hypoxic vasoconstriction in rat lungs. Am J Physiol 249: H741–H746PubMedGoogle Scholar
  49. 49.
    Tolins M, Weir E, Chesler E, Nelson D, From A (1986) Pulmonary vascular tone is increased by a voltage-dependent calcium channel potentiator. J Appl Physiol 60: 942–948PubMedGoogle Scholar
  50. 50.
    Post J, Hume J, Archer S, Weir E (1992) Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol 262: C882–C890PubMedGoogle Scholar
  51. 51.
    Thomas H, Carson R, Fried E, Novitch R (1991) Inhibition of hypoxic pulmonary vasoconstriction by diphenyleneiodonium. Biochem Pharm 42: R9–R12PubMedCrossRefGoogle Scholar
  52. 52.
    Weir E, Wyatt C, Reeve H, Huang J, Archer S, Peers C (1994) Diphenyleneiodonium inhibits both potassium and calcium currents in isolated pulmonary artery smooth muscle cells. J Appl Physiol 76: 2611–2615PubMedGoogle Scholar
  53. 53.
    Rounds S, McMurtry I (1981) Inhibitors of oxidative ATP production cause transient vasoconstriction and block subsequent pressor responses in rat lungs. Circ Res 48: 393–400PubMedGoogle Scholar
  54. 54.
    Buescher P, Pearse D, Pillai R, Litt M, Mitchell M, Sylvester J (1991) Energy state and vasomotor tone in hypoxic pig lungs. J Appl Physiol 70: 1874–1881PubMedCrossRefGoogle Scholar
  55. 55.
    Fisher AB, Dodia C (1981) Lung as a model for evaluation of critical intracellular PO2 and PCO. Am J Physiol 241: E47–E50PubMedGoogle Scholar
  56. 56.
    Youngson C, Nurse C, Yeger H, Cutz E (1993) Oxygen sensing in airway chemoreceptors. Nature 365: 153–155PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • S. Archer
  • E. K. Weir

There are no affiliations available

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