help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Data Supplement
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 Jankov, R. P.
Right arrow Articles by Tanswell, A. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jankov, R. P.
Right arrow Articles by Tanswell, A. K.
American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 208-214, (2002)
© 2002 American Thoracic Society

Original Article

Thromboxane A2 Receptors Mediate Pulmonary Hypertension in 60% Oxygen–exposed Newborn Rats by a Cyclooxygenase-independent Mechanism

Robert P. Jankov, Rosetta Belcastro, Emira Ovcina, Julia Lee, Hamid Massaeli, Stephen J. Lye and A. Keith Tanswell

Canadian Institutes of Health Research (CIHR) Group in Lung Development, Lung Biology Programme; Division of Cardiovascular Research, Hospital for Sick Children Research Institute; CIHR Group in Developmental and Fetal Health, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital; and Departments of Obstetrics and Gynaecology, Paediatrics, and Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Correspondence and requests for reprints should be addressed to Dr. A. Keith Tanswell, Division of Neonatology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8 Canada. E-mail: keitht{at}sickkids.ca

Endothelin-1 (ET-1) mediates the development of pulmonary hypertension (PHT) in newborn rats exposed to 60% O2 for 14 days, a model for human chronic neonatal lung injury. ET-1 production by d-14 rat pulmonary artery smooth muscle cells in vitro was markedly increased by thromboxane (TX) A2 receptor agonists and inhibited by a competitive antagonist. We hypothesized that stimulation of the TX A2 receptor contributed to O2-mediated PHT in vivo. Newborn rat pups received daily intraperitoneal injections of L670596, a competitive TX A2 receptor antagonist, or 5,5-dimethyl-3-(3-fluorophenyl)4-(4-methylsulfonyl)phenyl-2(5H)-furanone (DFU), a cyclooxygenase-2 inhibitor, during 14 days of 60% O2 or air exposure. L670596, but not DFU, prevented 60% O2–mediated right ventricular and small pulmonary vessel smooth muscle hypertrophy. Lung ET-1 content was significantly reduced by L670596 in 60% O2–exposed animals. We conclude that TX A2 receptor activation, though not by TX A2, caused upregulation of ET-1 and PHT in this model. A likely mediator is the stable lipid peroxidation product, 8-iso-prostane, which acts as an incidental ligand of the TX A2 receptor and is a potent inducer of ET-1 production by cultured d-14 rat pulmonary artery smooth muscle cells in vitro.

Key Words: endothelin-1 • 8-isoprostane • pulmonary oxygen toxicity • reactive oxygen species




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Masood, M. Yi, M. Lau, R. Belcastro, S. Shek, J. Pan, C. Kantores, P. J. McNamara, B. P. Kavanagh, J. Belik, et al.
Therapeutic effects of hypercapnia on chronic lung injury and vascular remodeling in neonatal rats
Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L920 - L930.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
L. J. Janssen
Isoprostanes and Lung Vascular Pathology
Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 383 - 389.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M.-C. Cathcart, R. Tamosiuniene, G. Chen, T. G. Neilan, A. Bradford, K. J. O'Byrne, D. J. Fitzgerald, and G. P. Pidgeon
Cyclooxygenase-2-Linked Attenuation of Hypoxia-Induced Pulmonary Hypertension and Intravascular Thrombosis
J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 51 - 58.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. P. Jankov, C. Kantores, J. Pan, and J. Belik
Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats
Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L233 - L245.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Hinton, A. Gutsol, and S. Dakshinamurti
Thromboxane hypersensitivity in hypoxic pulmonary artery myocytes: altered TP receptor localization and kinetics
Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L654 - L663.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. Kantores, P. J. McNamara, L. Teixeira, D. Engelberts, P. Murthy, B. P. Kavanagh, and R. P. Jankov
Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat
Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L912 - L922.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
C. D. Fike, Y. Zhang, and M. R. Kaplowitz
Thromboxane inhibition reduces an early stage of chronic hypoxia-induced pulmonary hypertension in piglets
J Appl Physiol, August 1, 2005; 99(2): 670 - 676.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. P. Jankov, C. Kantores, R. Belcastro, S. Yi, R. A. Ridsdale, M. Post, and A. K. Tanswell
A role for platelet-derived growth factor {beta}-receptor in a newborn rat model of endothelin-mediated pulmonary vascular remodeling
Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1162 - L1170.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
G. P. Pidgeon, R. Tamosiuniene, G. Chen, I. Leonard, O. Belton, A. Bradford, and D. J. Fitzgerald
Intravascular Thrombosis After Hypoxia-Induced Pulmonary Hypertension: Regulation by Cyclooxygenase-2
Circulation, October 26, 2004; 110(17): 2701 - 2707.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
J.-L. Cracowski and O. Ormezzano
Isoprostanes, emerging biomarkers and potential mediators in cardiovascular diseases
Eur. Heart J., October 1, 2004; 25(19): 1675 - 1678.
[Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. Belik, R. P. Jankov, J. Pan, M. Yi, C. R. Pace-Asciak, and A. K. Tanswell
Effect of 8-isoprostaglandin F2{alpha} on the newborn rat pulmonary arterial muscle and endothelium
J Appl Physiol, November 1, 2003; 95(5): 1979 - 1985.
[Abstract] [Full Text] [PDF]

Home page
 HeartHome page
J-L Cracowski
The putative role of isoprostanes in human cardiovascular physiology and disease: following the fingerprints
Heart, August 1, 2003; 89(8): 821 - 822.
[Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. Belik, R. P. Jankov, J. Pan, and A. K. Tanswell
Chronic O2 exposure enhances vascular and airway smooth muscle contraction in the newborn but not adult rat
J Appl Physiol, June 1, 2003; 94(6): 2303 - 2312.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Pediatrics, Surfactant, and Cystic Fibrosis in AJRCCM 2002
Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 333 - 344.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2002 American Thoracic Society 		  Membership Renewal