ERK1/2 signaling pathway is involved in 15-hydroxyeicosatetraenoic acid-induced hypoxic pulmonary vasoconstriction.
- Author:
Chang-Lian LÜ
1
;
Hong YE
;
Xiao-Bo TANG
;
Da-Ling ZHU
Author Information
1. College of Pharmacy, Harbin Medical University, Harbin 150086, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Flavonoids;
pharmacology;
Hydroxyeicosatetraenoic Acids;
antagonists & inhibitors;
pharmacology;
Hypoxia;
physiopathology;
MAP Kinase Signaling System;
physiology;
Male;
Muscle, Smooth, Vascular;
cytology;
Myocytes, Smooth Muscle;
drug effects;
Pulmonary Artery;
cytology;
drug effects;
physiopathology;
Rats;
Rats, Wistar;
Vasoconstriction;
drug effects
- From:
Acta Physiologica Sinica
2005;57(5):605-611
- CountryChina
- Language:English
-
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 (FIO2, 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.
