Hypoxia-induced reactive oxygen species downregulate ETBreceptor-mediated contraction of rat pulmonary arteries
Open Access
- 1 March 2006
- journal article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 290 (3) , L570-L578
- https://doi.org/10.1152/ajplung.00262.2005
Abstract
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 (ETB) receptor-mediated vasocontraction in lungs was determined. In rat intrapulmonary (∼0.63 mm ID) arteries, contraction induced by IRL-1620 (a selective ETBreceptor 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 ETBreceptor-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 ETBreceptor protein was reduced after 4 h of exposure to hypoxia, exogenous superoxide anions, or ET-1. BQ-788, a selective ETBreceptor 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 ETBreceptor-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 ETBreceptors on smooth muscle.Keywords
This publication has 48 references indexed in Scilit:
- Hypoxic pulmonary vasoconstriction: redox events in oxygen sensingJournal of Applied Physiology, 2005
- Extracellular Superoxide Dismutase Is a Major Determinant of Nitric Oxide BioavailabilityCirculation Research, 2003
- BQ‐788, A Selective Endothelin ETB Receptor AntagonistCardiovascular Drug Reviews, 2002
- Hypoxia promotes oxidative base modifications in the pulmonary artery endothelial cell VEGF geneThe FASEB Journal, 2001
- Oxidative Stress Increases Synthesis of Big Endothelin-1 by Activation of the Endothelin-1 PromoterJournal of Molecular and Cellular Cardiology, 2000
- DOWN-REGULATION OF ETb RECEPTOR, BUT NOT ETa RECEPTOR, IN CONGESTIVE LUNG SECONDARY TO HEART FAILURE. ARE MARKED INCREASES IN CIRCULATING ENDOTHELIN-1 PARTLY ATTRIBUTABLE TO DECREASES IN LUNG ETb RECEPTOR-MEDIATED CLEARANCE OF ENDOTHELIN-1?Life Sciences, 1997
- Effect of hypoxia and reoxygenation on the formation and release of reactive oxygen species by porcine pulmonary artery endothelial cellsJournal of Cellular Physiology, 1995
- Endothelin ETA- and ETB-Receptor-Mediated Vasoconstriction in Rat Pulmonary Arteries and ArteriolesJournal of Cardiovascular Pharmacology, 1994
- ETA and ETB Receptors Coexist on Rabbit Pulmonary Artery Vascular Smooth Muscle Mediating ContractionBiochemical and Biophysical Research Communications, 1993
- A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptorBiochemical and Biophysical Research Communications, 1992