HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/L570    most recent 00262.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Wang, X. Articles by Gao, Y. Search for Related Content PubMed PubMed Citation Articles by Wang, X. Articles by Gao, Y.

Hypoxia-induced reactive oxygen species downregulate ET_B receptor-mediated contraction of rat pulmonary arteries

¹Department of Physiology and Pathophysiology, Peking University Health Science Center, ²Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing 100083, China; and ³Division of Neonatology, Harbor-UCLA Medical Center, Geffen School of Medicine at University of California, Los Angeles, and Los Angeles Biomedical Research Institute, Los Angeles, California

Submitted 17 June 2005 ; accepted in final form 6 October 2005

Production of reactive oxygen species (ROS) may be increased during hypoxia in pulmonary arteries. In this study, the role of ROS in the effect of hypoxia on endothelin (ET) type B (ET_B) receptor-mediated vasocontraction in lungs was determined. In rat intrapulmonary (0.63 mm ID) arteries, contraction induced by IRL-1620 (a selective ET_B receptor agonist) was significantly attenuated after 4 h of hypoxia (30 mmHg PO₂) compared with normoxic control (140 mmHg PO₂). The effect was abolished by tiron, a scavenger of superoxide anions, but not by polyethylene glycol (PEG)-conjugated catalase, which scavenges H₂O₂. The hypoxic effect on ET_B receptor-mediated vasoconstriction was also abolished by endothelium denudation but not by nitro-L-arginine and indomethacin. Exposure for 4 h to exogenous superoxide anions, but not H₂O₂, attenuated the vasoconstriction induced by IRL-1620. Confocal study showed that hypoxia increased ROS production in pulmonary arteries that were scavenged by PEG-conjugated SOD. In endothelium-intact pulmonary arteries, the ET_B receptor protein was reduced after 4 h of exposure to hypoxia, exogenous superoxide anions, or ET-1. BQ-788, a selective ET_B receptor antagonist, prevented these effects. ET-1 production was stimulated in endothelium-intact arteries after 4 h of exposure to hypoxia or exogenous superoxide anions. This effect was blunted by PEG-conjugated SOD. These results demonstrate that exposure to hypoxia attenuates ET_B receptor-mediated contraction of rat pulmonary arteries. A hypoxia-induced production of superoxide anions may increase ET-1 release from the endothelium and result in downregulation of ET_B receptors on smooth muscle.

superoxide; endothelin

This article has been cited by other articles:

				N. L. Jernigan, B. R. Walker, and T. C. Resta Reactive oxygen species mediate RhoA/Rho kinase-induced Ca2+ sensitization in pulmonary vascular smooth muscle following chronic hypoxia Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L515 - L529. [Abstract] [Full Text] [PDF]

				W. Wu, O. Platoshyn, A. L. Firth, and J. X.-J. Yuan Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L952 - L959. [Abstract] [Full Text] [PDF]