help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on January 30, 2004, doi:10.1165/rcmb.2003-0287OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 6, June 2004, 908-913

A more recent version of this article appeared on June 1, 2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2003-0287OCv1
30/6/908    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hassoun, P. M
Right arrow Articles by Bloch, K. D
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hassoun, P. M
Right arrow Articles by Bloch, K. D

Submitted on July 31, 2003
Revised on January 30, 2004

Hypoxia Decreases Soluble Guanylate Cyclase Expression in Pulmonary Artery Smooth Muscle Cells

Paul M Hassoun1*, Galina Filippov2, Michael Fogel3, Cameron Donaldson3, Usamah S Kayyali3, Larissa A Shimoda1, and Kenneth D Bloch2

1 Medicine, Johns Hopkins, Baltimore, Maryland, USA, 2 Medicine, Massachusetts General Hospital, Boston, Massachussets, USA, 3 Medicine, Tufts University School of Medicine, Boston, Massachussets, USA

* To whom correspondence should be addressed. E-mail: phassoun{at}jhmi.edu.

Nitric oxide (NO) has an important role in modulating the pulmonary vascular tone. NO acts, in part, by stimulating soluble guanylate cyclase (sGC) to synthesize the intracellular second messenger cGMP. In vascular smooth muscle cells, sGC is a heterodimer composed of {alpha}1 and {beta}1 subunits. The objective of this study was to test whether oxygen concentration regulates sGC expression in cultured rat pulmonary artery smooth muscle cells (rPaSMC). rPaSMC were exposed to 0, 3, and 20% oxygen for 1 to 48 hours, and sGC subunit mRNA levels were measured. Compared with rPaSMC exposed to 20% oxygen, sGC {alpha}1 and {beta}1 subunit mRNA levels were markedly decreased in rPaSMC exposed to 0% and 3% oxygen. The decrease in sGC subunit mRNA levels in hypoxic rPaSMC was detected as early as 6 hours of exposure. Compared with rPaSMC exposed to 20% oxygen, exposure of rPaSMC to 3% oxygen progressively decreased sGC subunit protein levels at 24 and 48 hours. There was also a 30% and 50% decrease in sGC enzyme activity in cells exposed to hypoxia for 24 and 48 hours (P <0.05 and P <0.001, respectively, as compared to cells maintained in normoxia). These results demonstrate that hypoxia decreases sGC expression in cultured pulmonary artery smooth muscle cells and suggest that, in hypoxic vascular smooth muscle, decreased cGMP synthesis may limit the vasodilator response to NO.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. L. Marro, C. Peiro, C. M. Panayiotou, R. S. Baliga, S. Meurer, H. H. H. W. Schmidt, and A. J. Hobbs
Characterization of the Human {alpha}1{beta}1 Soluble Guanylyl Cyclase Promoter: KEY ROLE FOR NF-{kappa}B(p50) AND CCAAT-BINDING FACTORS IN REGULATING EXPRESSION OF THE NITRIC OXIDE RECEPTOR
J. Biol. Chem., July 18, 2008; 283(29): 20027 - 20036.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
Q. Xue, C. A. Ducsay, L. D. Longo, and L. Zhang
Effect of long-term high-altitude hypoxia on fetal pulmonary vascular contractility
J Appl Physiol, June 1, 2008; 104(6): 1786 - 1792.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. J. Mingone, M. Ahmad, S. A. Gupte, J. L. Chow, and M. S. Wolin
Heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide
Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1244 - H1250.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. He, J. Chen, X. Liu, B. Dinger, and S. Fidone
Enhanced nitric oxide-mediated chemoreceptor inhibition and altered cyclic GMP signaling in rat carotid body following chronic hypoxia
Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1463 - L1468.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. P. Coggins and K. D. Bloch
Nitric Oxide in the Pulmonary Vasculature
Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1877 - 1885.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. Oka, V. Karoor, N. Homma, T. Nagaoka, E. Sakao, S. M. Golembeski, J. Limbird, M. Imamura, S. A. Gebb, K. A. Fagan, et al.
Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension
Cardiovasc Res, June 1, 2007; 74(3): 377 - 387.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. J. Mingone, S. A. Gupte, J. L. Chow, M. Ahmad, N. G. Abraham, and M. S. Wolin
Protoporphyrin IX generation from {delta}-aminolevulinic acid elicits pulmonary artery relaxation and soluble guanylate cyclase activation.
Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L337 - L344.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. M. Williams, C. R. White, M. M. Chang, E. R. Injeti, L. Zhang, and W. J. Pearce
Chronic hypoxic decreases in soluble guanylate cyclase protein and enzyme activity are age dependent in fetal and adult ovine carotid arteries
J Appl Physiol, June 1, 2006; 100(6): 1857 - 1866.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. J. Mingone, S. A. Gupte, N. Ali, R. A. Oeckler, and M. S. Wolin
Thiol oxidation inhibits nitric oxide-mediated pulmonary artery relaxation and guanylate cyclase stimulation
Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L549 - L557.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. Dumitrascu, N. Weissmann, H. A. Ghofrani, E. Dony, K. Beuerlein, H. Schmidt, J.-P. Stasch, M. J. Gnoth, W. Seeger, F. Grimminger, et al.
Activation of Soluble Guanylate Cyclase Reverses Experimental Pulmonary Hypertension and Vascular Remodeling
Circulation, January 17, 2006; 113(2): 286 - 295.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2004 American Thoracic Society. 		  ATS Best of the Web