AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 281: L941-L948, 2001;
1040-0605/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Carpenter, T. C.
Right arrow Articles by Stenmark, K. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carpenter, T. C.
Right arrow Articles by Stenmark, K. R.
Vol. 281, Issue 4, L941-L948, October 2001

Hypoxia decreases lung neprilysin expression and increases pulmonary vascular leak

Todd C. Carpenter and Kurt R. Stenmark

Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262

Although prior studies suggest that hypoxia may increase pulmonary vascular permeability, the mechanisms responsible for that effect remain uncertain. Neprilysin (neutral endopeptidase) is a cell surface metallopeptidase that degrades several vasoactive peptides including substance P and bradykinin. We hypothesized that hypoxia could reduce lung neprilysin expression, leading to increased vascular leak. Weanling rats were exposed to normobaric hypoxia (inspired O2 fraction = 0.1). Lung neprilysin activity was significantly decreased after 24 and 48 h of hypoxia (P < 0.006). The decrease in enzyme activity was associated with decreased lung neprilysin protein content and decreased lung neprilysin mRNA expression. Immunohistochemistry showed a predominantly perivascular distribution of neprilysin, with clear reductions in neprilysin immunoreactivity after exposure to hypoxia. Exposure to hypoxia for 24 h also caused marked increases in vascular leak (P = 0.008), which were reversed by the administration of recombinant neprilysin. The hypoxia-induced increase in leak was also reversed by substance P and bradykinin receptor antagonists. We conclude that in young rats hypoxia decreases lung neprilysin expression, which contributes to increased pulmonary vascular leak via substance P and bradykinin receptors.

pulmonary edema; neurokinin-1 receptor; substance P; bradykinin


This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Loffler, J. C. Morote-Garcia, S. A. Eltzschig, I. R. Coe, and H. K. Eltzschig
Physiological Roles of Vascular Nucleoside Transporters
Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1004 - 1013.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. D. Zee, S. Schomberg, and T. C. Carpenter
Hypoxia upregulates lung microvascular neurokinin-1 receptor expression
Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L102 - L110.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. C. Irwin, M. C. Tissot van Patot, A. Tucker, and R. Bowen
Direct ANP inhibition of hypoxia-induced inflammatory pathways in pulmonary microvascular and macrovascular endothelial monolayers
Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L849 - L859.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
H. K. Eltzschig, J. C. Ibla, G. T. Furuta, M. O. Leonard, K. A. Jacobson, K. Enjyoji, S. C. Robson, and S. P. Colgan
Coordinated Adenine Nucleotide Phosphohydrolysis and Nucleoside Signaling in Posthypoxic Endothelium: Role of Ectonucleotidases and Adenosine A2B Receptors
J. Exp. Med., September 2, 2003; 198(5): 783 - 796.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Duggan, C. L. McCaul, P. J. McNamara, D. Engelberts, C. Ackerley, and B. P. Kavanagh
Atelectasis Causes Vascular Leak and Lethal Right Ventricular Failure in Uninjured Rat Lungs
Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1633 - 1640.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online