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

American Journal of Physiology - Lung Cellular and Molecular Physiology - Tập 290 Số 3 - Trang L570-L578 - 2006
Xiaohua Wang, Mei Song Tong1, Shashi Chinta2, J. Usha Raj, Yuansheng Gao1
1Peking University
2University of California at, Los Angeles

Tóm tắt

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.

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American Journal of Physiology - Lung Cellular and Molecular Physiology

Tập 290 Số 3

L570-L578

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