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ERK1/2 signaling pathway is involved in 15--hydroxyeicosatetraenoic acid--induced hypoxic pulmonary vosoconstriction

Lu Changlian, Ye Hong, Tang Xiaobo, Zhu Daling

College of Pharmacy, Harbin Medical University.Harbin 150086,Heilongjiang；China；Key Laboratory of Biopharmaceutical Engineering of Heilongjiang Province.Harbin 150086,Heilongjiang

Abstract

Hypoxia-induced 15-hydroxyeicosatetraenoic acid (15-HETE) is an essential mediator to constrict pulmonary arteries (PA). The signaling pathway involved in 15-HETE-induced PA vasoconstriction remains obscure. The aim of the present study was to test the hypothesis that hypoxic PA constriction induced by 15-HETE was possibly regulated by the extracellular signal-regulated kinase-1/2 (ERK1/2) pathway. PA ring tension measurement, Western blot and immunocytochemistry were used in the study to determine the possible role of ERK1/2 in 15-HETE-induced PA vasoconstriction. The organ bath for PA rings tension study was employed. Adult male Wistar rats were raised in hypoxic environment with fractional inspired oxygen (FIO_(2), 0.12) for 9 d. PA 1--1.5 mm in diameter were dissected and cut into 3 mm long rings for tension study. ERK1/2 up-stream kinase (MEK) inhibitor PD98059, which blocks the activation of ERK1/2, was used. The results showed that pretreatment of PD98059 significantly blunted 15-HETE-induced PA vasoconstrictions in the rings from hypoxic rat. Moreover, in endothelium-denuded rings, PD98059 also significantly attenuated 15-HETE-induced vasoconstriction. Phosphorylation of ERK1/2 in pulmonary arterial smooth muscle cells (PASMCs) of rat was enhanced evidently when stimulated by 15-HETE. Thus, the data suggest that ERK1/2 signaling pathway is involved in 15-HETE-induced hypoxic pulmonary vasoconstriction.

Key words: Hypoxia;15-hydroxyeicosatetraenoic acid;15-lipoxygenase;extracellular signal-regulated kinase

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Citing This Article：

Lu Changlian, Ye Hong, Tang Xiaobo, Zhu Daling. ERK1/2 signaling pathway is involved in 15--hydroxyeicosatetraenoic acid--induced hypoxic pulmonary vosoconstriction . Acta Physiol Sin 2005; 57 (5): (in Chinese with English abstract).