ERK1/2 signaling pathway is involved in 15-hydroxyeicosatetraenoic acid-induced hypoxic pulmonary vasoconstriction.
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.
Lü
Chang-Lian
CL
College of Pharmacy, Harbin Medical University, Harbin 150086, China.
Ye
Hong
H
Tang
Xiao-Bo
XB
Zhu
Da-Ling
DL
D000818:Animals; D005419:Flavonoids / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects
D005419:Flavonoids; D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one