| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Division of Pulmonary and Critical Care, Department of Medicine, Duke University Medical Center, Durham 27710; and 2 Environmental Protection Agency, Chapel Hill, North Carolina 27599
Heme oxygenase (HO)-1 is an oxygen-dependent enzyme that may regulate vascular tone and cell proliferation through the production of carbon monoxide (CO). We tested the hypothesis that HO-1 is upregulated in the lung in chronic hypoxia by exposing male Sprague-Dawley rats to 17,000 feet (395 Torr) for 0, 1, 3, 7, 14, or 21 days. After exposure, blood gases, carboxyhemoglobin (COHb) levels, and hematocrit were measured, and the lungs were either inflation fixed for immunohistochemistry or frozen for later measurement of HO enzyme activity, Western blot for HO-1 protein, and RT-PCR for HO-1 mRNA. The heart was excised and weighed, and the right-to-left heart weight ratio was determined. During hypoxia, the hematocrit increased progressively, reaching significantly higher values than the control value after 3 days. COHb levels increased above the control value after 1 day of hypoxia and increased progressively between 14 and 21 days, whereas arterial PO2 and arterial PCO2 did not vary significantly. HO-1 protein determined by Western blot increased for the first 7 days and declined thereafter; however, enzyme activity was elevated only after 1 day. Changes in HO-1 during hypoxia were localized by immunohistochemistry to inflammatory cells (early) and newly muscularized arterioles (later). Lung HO-1 mRNA normalized to glyceraldehyde-3-phosphate dehydrogenase was increased after 1 and 21 days. The data indicate that lung HO-1 protein and activity are upregulated only during early chronic hypoxia, whereas persistent COHb elevations indicate high endogenous CO production rates at nonpulmonary sites. If CO has antiproliferative properties, the lack of HO enzyme activity in the lung may be permissive for pulmonary vascular proliferation in hypoxia.
pulmonary hypertension; hypoxic pulmonary vasoconstriction; carbon monoxide; adaptation
This article has been cited by other articles:
|
|
 |
|
  J. Sunderram, J. Semmlow, S. Thakker-Varia, M. Bhaumik, O. Hoang-Le, and J. A. Neubauer Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic hypoxia in mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R300 - R312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Herrera, R. V. Reyes, D. A. Giussani, R. A. Riquelme, E. M. Sanhueza, G. Ebensperger, P. Casanello, N. Mendez, R. Ebensperger, E. Sepulveda-Kattan, et al. Carbon monoxide: a novel pulmonary artery vasodilator in neonatal llamas of the Andean altiplano Cardiovasc Res, January 1, 2008; 77(1): 197 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dubuis, M. Potier, R. Wang, and C. Vandier Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BKCa channels Cardiovasc Res, February 15, 2005; 65(3): 751 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Hartsfield, I. F. McMurtry, D. D. Ivy, K. G. Morris, S. Vidmar, D. M. Rodman, and K. A. Fagan Cardioprotective and vasomotor effects of HO activity during acute and chronic hypoxia Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2009 - H2015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L Atzori, F Chua, S E Dunsmore, D Willis, M Barbarisi, R J McAnulty, and G J Laurent Attenuation of bleomycin induced pulmonary fibrosis in mice using the heme oxygenase inhibitor Zn-deuteroporphyrin IX-2,4-bisethylene glycol Thorax, March 1, 2004; 59(3): 217 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Nozik-Grayck, Y.-C. T. Huang, M. S. Carraway, and C. A. Piantadosi Bicarbonate-dependent superoxide release and pulmonary artery tone Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2327 - H2335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Naik, T. L. O'Donaughy, and B. R. Walker Endogenous carbon monoxide is an endothelial-derived vasodilator factor in the mesenteric circulation Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H838 - H845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Yang, D. J. Haile, F. G. Berger, D. C. Herbert, E. Van Beveren, and A. J. Ghio Haptoglobin reduces lung injury associated with exposure to blood Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L402 - L409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Jean, Y. Liu, L. A. Brown, R. E. Marc, E. Klings, and M. Joyce-Brady gamma -Glutamyl transferase deficiency results in lung oxidant stress in normoxia Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L766 - L776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-L. Giles, H. Suliman, L. B. Mamo, C. A. Piantadosi, T. D. Oury, and E. Nozik-Grayck Prenatal hypoxia decreases lung extracellular superoxide dismutase expression and activity Am J Physiol Lung Cell Mol Physiol, September 1, 2002; 283(3): L549 - L554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Dubuis, M. Gautier, A. Melin, M. Rebocho, C. Girardin, P. Bonnet, and C. Vandier Chronic carbon monoxide enhanced IbTx-sensitive currents in rat resistance pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L120 - L129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Appleton, G. S. Marks, K. Nakatsu, J. F. Brien, G. N. Smith, and C. H. Graham Heme oxygenase activity in placenta: direct dependence on oxygen availability Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2055 - H2059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Naik and B. R. Walker Homogeneous segmental profile of carbon monoxide-mediated pulmonary vasodilation in rats Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1436 - L1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mazza, S. Thakkar-Varia, C. A. Tozzi, and J. A. Neubauer Expression of heme oxygenase in the oxygen-sensing regions of the rostral ventrolateral medulla J Appl Physiol, July 1, 2001; 91(1): 379 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Otterbein and A. M. K. Choi Heme oxygenase: colors of defense against cellular stress Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1029 - L1037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Carraway, A. J. Ghio, H. B. Suliman, J. D. Carter, A. R. Whorton, and C. A. Piantadosi Carbon monoxide promotes hypoxic pulmonary vascular remodeling Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L693 - L702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Appleton, G. S. Marks, K. Nakatsu, J. F. Brien, G. N. Smith, and C. H. Graham Heme oxygenase activity in placenta: direct dependence on oxygen availability Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2055 - H2059. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
