Role of ERK1/2 signaling pathways in 4-aminopyridine-induced rat pulmonary vasoconstriction

The aim of the present study was to investigate the contribution of extracellular signal regulated kinase-1/2 (ERK1/2) to pulmonary artery contraction in response to 4-aminopyridione (4-AP), an inhibitor of a voltage-gated K+ channels that regulate pulmonary vascular tone. Pulmonary artery rings 1-1.5 mm in diameter from male adult Wistar rat were isolated and cut into 3-mm in length. ERK1/2 up-stream kinase (MEK) inhibitors 2'-amino-3'-methoxyflavone (PD98059) and 1,4-diamino-2,3-dicyano-1,4-bis (2-aminophenylthio)-butadiene (U0126), which block the activation of ERK1/2, were used to test the role of ERKI/2 in 4-AP induced pulmonary arterial vasoconstriction and the influences of 4-AP on expressions of phosphorylated ERK1/2 (p-ERK1/2) in cultured ratpulmonary arterial smooth muscle cells (PASMCs) and whole tissues. Our results show that 4-AP elicited concentration-dependent increases in tension of rat pulmonary artery rings, effects that were reduced by pretreatment of the rings with ERK inhibitors, PD98059 (20 mu M) and U0126 (10 mu M). Moreover, 4-AP increased the expressions of p-ERK1/2 in cultured PASMCs s and whole tissues, which were prevented by pretreatment of the cells or tissues with U0126. These results indicate that ERKI/2 signaling pathway contributes to pulmonary vasoconstriction induced by 4-AP. (c) 2007 Elsevier B.V. All rights reserved.