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 ERK1/2 in 4-AP induced pulmonary arterial vasoconstriction and the influences of 4-AP on expressions of phosphorylated ERK1/2 (p-ERK1/2) in cultured rat pulmonary 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 microM) and U0126 (10 microM). 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 ERK1/2 signaling pathway contributes to pulmonary vasoconstriction induced by 4-AP.