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Redox Signaling in Hypoxic Pulmonary Vasoconstriction

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Abstract

Changes in oxygen tension are sensed by a variety of tissues, such as the carotid body, ductus arteriosus (DA), and pulmonary vasculature. In the fetus, hypoxia keeps the DA open and the pulmonary vessels constricted. After birth, hypoxic pulmonary vasoconstriction (HPV) helps to match ventilation and perfusion. HPV is induced by three general mechanisms—influx of calcium into the smooth muscle cells through L-type channels and store-operated channels, release of calcium from the sarcoplasmic reticulum, and sensitization of actin/myosin to a given level of calcium. We show that reducing agents mimic the effects of hypoxia by reducing potassium current, causing membrane depolarization and increasing calcium influx in pulmonary artery smooth muscle cells (PASMCs), while doing exactly the opposite in the DA. On the other hand, oxidizing agents mimic normoxia by increasing potassium current, causing membrane hyperpolarization and reducing cytosolic calcium in PASMCs. They again do the opposite in the DA. As these redox agents elicit the same responses as shifts in oxygen tension, we consider that changes in oxygen may be signaled by changes in redox status.

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References

  1. Lopez-Barneo, J., Lopez-Lopez, J., Urena, J., et al. (1988) Chemotransduction in the carotid body: K+ current modulated by Po2 in type I chemoreceptor cells. Science 242, 580–582.

    Article  Google Scholar 

  2. Zhu, W., Conforti, L., Czyzyk-Krzeska, M., et al. (1996) Membrane depolarization in PC12 cells during hypoxia is regulated by an O2-sensitive K+ current. Am. J. Physiol. 40, C568–C665.

    Google Scholar 

  3. Fearon, I., Thompson, R., Samjoo, I., et al. (2002) O2-sensitive K+ channels in immortalised rat chromaffin-cell-derived MAH cells. J. Physiol. 545.3, 807–818.

    Article  CAS  Google Scholar 

  4. Youngson, C., Nurse, C., Yeger, H., et al. (1993) Oxygen sensing in airway chemoreceptors. Nature 365, 153–155.

    Article  CAS  PubMed  Google Scholar 

  5. O’Kelly, I., Lewis, A., Peers, C., et al. (2000) O2 sensing by airway chemoreceptor-derived cells. J. Biol. Chem. 275, 7684–7692.

    Article  CAS  PubMed  Google Scholar 

  6. Shirai, M., Sada, K., and Niromiya, I. (1986) Effects of regional alveodar hypoxia and hypercapnia on small pulmonary vessels in cats. J. Appl. Physiol. 61, 440–448.

    CAS  PubMed  Google Scholar 

  7. Jensen, K., Mico, A., Czartolomna, J., et al. (1992) Rapid onset of hypoxic vasoconstriction in isolated lings. J. Appl. Physiol. 72, 2018–2033.

    CAS  PubMed  Google Scholar 

  8. Reeves, J. and Grover, R. (1974) Blockade of acute hypoxic pulmonary hypertension by endotoxin. J. Appl. Physiol. 36, 328–332.

    CAS  PubMed  Google Scholar 

  9. Weir, E., Tierney, J., Chesler, E., et al. (1983) Zymosan activation of plasma reduces hypoxic pulmonary vasoconstriction. Resp. Physiol. 53, 295–306.

    Article  CAS  Google Scholar 

  10. Salvaterra, C. and Goldman, W. (1993) Acute hypoxia increases cytosolic calcium in cultured pulmonary srterial myocytes. Am. J. Physiol. 264, L323–L328.

    CAS  PubMed  Google Scholar 

  11. Olschewski, A., Hong, Z., Nelson, D., et al. (2002) Graded response of K+ current, membrane potential and [Ca2+]i to hypoxia in pulmonary arterial smooth muscle.Am. J. Physiol. Lung Cell Mol. Physiol. 283, L1143–L1150.

    CAS  PubMed  Google Scholar 

  12. Tristani-Firouzi, M., Reeve, H., Tolarova, S., et al. (1996) Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel. J. Clin. Invest. 98, 1959–1965.

    Article  CAS  PubMed  Google Scholar 

  13. Michelakis, E., Rebeyka, I., Wu, X., et al. (2002) O2 sensing in the human ductus arteriosus. Circ. Res. 91, 478–486.

    Article  CAS  PubMed  Google Scholar 

  14. Archer, S., Will, J., and Weir, E. (1986) Redox status in the control of pulmonary vascular tone. Herz 11, 127–141.

    CAS  PubMed  Google Scholar 

  15. Archer, S., Huang, J., Henry, T., et al. (1993) A redox-based O2 sensor in rat pulmonary vasculature. Circ. Res. 73, 1100–1112.

    CAS  PubMed  Google Scholar 

  16. Archer, S., Reeve, H., Michelakis, E., et al. (1999) O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Proc. Natl. Acad. Sci. USA 96, 7944–7949.

    Article  CAS  PubMed  Google Scholar 

  17. Post, J., Weir, E., Archer, S., et al. (1993) Redox regulation of K+ channels and hypoxic pulmonary vasoconstriction. In: Weir, E. K., Hume, J. R., and Reeves, J. T. (eds), Ion Flux in Pulmonary Vascular Control. Plenum, New York, pp. 189–204.

    Google Scholar 

  18. Reeve, H., Weir, E., Nelson, D., et al. (1995) Opposing effects of oxidants and antioxidants on K+ channel activity and tone in rat vascular tissue. Exp. Physiol. 80, 825–834.

    CAS  PubMed  Google Scholar 

  19. Yuan, X-J., Tod, M., Rubin, L., et al. (1994) Deoxyglucose and reduced glutathione mimic effects of hypoxia on K+ and Ca2+ conductances in pulmonary artery cells. Am. J. Physiol. 2994, L52–L63.

    Google Scholar 

  20. Weir, E. and Archer, S. (1995) The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. FASEB J. 9, 183–189.

    CAS  PubMed  Google Scholar 

  21. Park, M., Lee, S., Lee, S., et al. (1995) Different modulation of Ca-activated K channels by the intracellular redox potential in pulmonary and ear arterial smooth muscle cells of the rabbit. Eur. J. Physiol. 430, 308–314.

    Article  CAS  Google Scholar 

  22. Reeve, H., Michelakis, E., Nelson, D., et al. (2001) Alterations in a redox oxygen sensing mechanism in chronic hypoxia. J. Appl. Physiol. 90, 2249–5226.

    CAS  PubMed  Google Scholar 

  23. Olschewski, A., Hong, Z., Peterson, D., et al. (2004) 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. 286, L15–L22.

    Article  CAS  PubMed  Google Scholar 

  24. Wang, D., Youngson, C., Wong, V., et al. (1996) NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines. Proc. Natl. Acad. Sci. USA 93, 13182–13187.

    Article  CAS  PubMed  Google Scholar 

  25. Fu, X., Nurse, C., and Wang, Y. (1999) Selective modulation of membrane currents by hypoxia in intact airway chemoreceptors from neonatal rabbit. J. Physiol. 514, 139–150.

    Article  CAS  PubMed  Google Scholar 

  26. Reeve, H., Tolarova, S., Nelson, D., et al. (2001) Redox control of oxygen sensing in the rabbit ductus arteriosus. J. Physiol. 533.1, 253–261.

    Article  Google Scholar 

  27. Chander, A., Dhariwal, K., and Viswanathan, R. (1980) Pyridine nucleotides in lung and liver of hypoxic rats. Life Sci. 26, 1935–1945.

    Article  CAS  PubMed  Google Scholar 

  28. Baxter, L., Snetkov, V., Aaronson, P., et al. (2002) Pulmonary and systemic vascular smooth muscle demonstrate differential sensitivity to hypoxia in terms of the rise in mitochondrial NAD(P)H. J. Physiol. 544P, S030.

    Google Scholar 

  29. Weir, E. K., Hong, Z., Porter, V., and Reeve, E. (2002) Redox signaling in oxygen sensing by vessels. Resp. Physiol. Neurobiol. 132, 121–130.

    Article  CAS  Google Scholar 

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© 2005 Humana Press Inc., Totowa, NJ

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Weir, E.K., Hong, Z., Varghese, A., Nelson, D.P., Olschewski, A. (2005). Redox Signaling in Hypoxic Pulmonary Vasoconstriction. In: Bhattacharya, J. (eds) Cell Signaling in Vascular Inflammation. Humana Press. https://doi.org/10.1007/978-1-59259-909-7_4

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  • DOI: https://doi.org/10.1007/978-1-59259-909-7_4

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-525-5

  • Online ISBN: 978-1-59259-909-7

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