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

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 (approximately 0.63 mm ID) arteries, contraction induced by IRL-1620 (a selective ETB 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 ETB 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 ETB receptor protein was reduced after 4 h of exposure to hypoxia, exogenous superoxide anions, or ET-1. BQ-788, a selective ETB 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 ETB 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 ETB receptors on smooth muscle.

• Authors: Xiaohua Wang, Mei Tong, Shashi Chinta, J Usha Raj, Yuansheng Gao
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 290 Issue 3 Pg. L570-8 (Mar 2006) ISSN: 1040-0605 [Print] United States
• PMID: 16227321 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Endothelins
• Peptide Fragments
• Reactive Oxygen Species
• Receptor, Endothelin B
• Superoxides
• sovateltide

Topics

• Animals
• Down-Regulation
• Endothelin-1 (pharmacology)
• Endothelins (pharmacology)
• Endothelium, Vascular (drug effects, metabolism)
• Hypertension, Pulmonary (complications, metabolism)
• Hypoxia (metabolism)
• Lung (drug effects, metabolism)
• Male
• Muscle Contraction (drug effects)
• Muscle, Smooth, Vascular (metabolism)
• Peptide Fragments (pharmacology)
• Pulmonary Artery (metabolism)
• Pulmonary Circulation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Receptor, Endothelin B (metabolism)
• Superoxides (metabolism)
• Vasoconstriction (physiology)