Published ahead of print on December 15, 2005, doi:10.1165/rcmb.2005-0337OC
Am. J. Respir. Cell Mol. Biol., Volume 34, Number 4, April 2006, 505-513
A more recent version of this article appeared on April 1, 2006
Submitted on September 2, 2005
Revised on December 15, 2005
Impact of Mitochondria and NADPH Oxidases on Acute and Sustained Hypoxic Pulmonary Vasoconstriction
Norbert Weissmann1*, Stefanie Zeller1, Rolf U Schafer1, Carmen Turowski1, Mahmut Ay1, Karin Quanz1, Hossein A Ghofrani1, Ralph T Schermuly1, Ludger Fink2, Werner Seeger1, and Friedrich Grimminger1
1 Department of Internal Medicine II/V, Justus-Liebig-University Giessen, Giessen, Germany,
2 Institute of Pathology, Justus-Liebig-University Giessen, Giessen, Germany
* To whom correspondence should be addressed. E-mail: Norbert.Weissmann{at}uglc.de.
Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation to optimize pulmonary gas exchange. However, it remains unclear whether acute HPV (occurring within seconds) and the vasoconstrictor response to sustained alveolar hypoxia (developing over several hours) are triggered by identical mechanisms. We investigated the effect of mitochondrial and NADPH oxidase inhibitors on both phases of HPV in intact rabbit lungs. These studies revealed that the sustained HPV is largely dependent on mitochondrial complex I and totally dependent on complex IV, whereas NADPH oxidase-dependence was only observed for acute HPV. These findings were reinforced by an alternative approach employing lungs from mice deficient in the NADPH oxidase subunit p47phox. In these mice, which lack a subunit suggested to be important for the function of most NADPH oxidase isoforms, but not in gp91phox deficient mice which represent only one isoform of NADPH oxidases, acute HPV was significantly reduced while non-hypoxia-induced vasoconstrictions elicited by the thromboxane mimetic U46619 were not affected. We concluded that the acute phase and the sustained phase of HPV are differentially regulated, with NADPH oxidase activity predominating in the acute phase, while a strong dependence on mitochondrial participation was observed for the second phase.
This article has been cited by other articles:
|
|
|
|
 
K. B. Adler and S. Matalon
Highlights of the May Issue
Am. J. Respir. Cell Mol. Biol.,
May 1, 2009;
40(5):
505 - 506.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Nisbet, A. S. Graves, D. J. Kleinhenz, H. L. Rupnow, A. L. Reed, T.-H. M. Fan, P. O. Mitchell, R. L. Sutliff, and C. M. Hart
The Role of NADPH Oxidase in Chronic Intermittent Hypoxia-Induced Pulmonary Hypertension in Mice
Am. J. Respir. Cell Mol. Biol.,
May 1, 2009;
40(5):
601 - 609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Cogolludo, L. Moreno, G. Frazziano, J. Moral-Sanz, C. Menendez, J. Castaneda, C. Gonzalez, E. Villamor, and F. Perez-Vizcaino
Activation of neutral sphingomyelinase is involved in acute hypoxic pulmonary vasoconstriction
Cardiovasc Res,
May 1, 2009;
82(2):
296 - 302.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Sommer, A. Dietrich, R. T. Schermuly, H. A. Ghofrani, T. Gudermann, R. Schulz, W. Seeger, F. Grimminger, and N. Weissmann
Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms
Eur. Respir. J.,
December 1, 2008;
32(6):
1639 - 1651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tabuchi, M. Mertens, H. Kuppe, A. R. Pries, and W. M. Kuebler
Intravital microscopy of the murine pulmonary microcirculation
J Appl Physiol,
February 1, 2008;
104(2):
338 - 346.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mittal, M. Roth, P. Konig, S. Hofmann, E. Dony, P. Goyal, A.-C. Selbitz, R. T. Schermuly, H. A. Ghofrani, G. Kwapiszewska, et al.
Hypoxia-Dependent Regulation of Nonphagocytic NADPH Oxidase Subunit NOX4 in the Pulmonary Vasculature
Circ. Res.,
August 3, 2007;
101(3):
258 - 267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. K. Weir and S. L. Archer
COUNTERPOINT: HYPOXIC PULMONARY VASOCONSTRICTION IS NOT MEDIATED BY INCREASED PRODUCTION OF REACTIVE OXYGEN SPECIES
J Appl Physiol,
September 1, 2006;
101(3):
995 - 998.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Rebuttal from drs. Weir and archer.
J Appl Physiol,
September 1, 2006;
101(3):
999 - 999.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. T. Ward
Last Word: Point:Counterpoint authors respond to commentaries on "Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of reactive oxygen species"
J Appl Physiol,
September 1, 2006;
101(3):
1004 - 1004.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. K. Weir and A. Olschewski
Role of ion channels in acute and chronic responses of the pulmonary vasculature to hypoxia
Cardiovasc Res,
September 1, 2006;
71(4):
630 - 641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Acker, J. Fandrey, and H. Acker
The good, the bad and the ugly in oxygen-sensing: ROS, cytochromes and prolyl-hydroxylases
Cardiovasc Res,
July 15, 2006;
71(2):
195 - 207.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2005 American Thoracic Society.
|
|
|
