Role of protein kinase C in 15‐HETE‐induced hypoxic pulmonary vasoconstriction

Abstract

AbstractThe aim of the present study was to investigate the roles of protein kinase C (PKC) signal transduction pathways in the 15‐hydroxyeicosatetraenoic acid (15‐HETE)‐induced down‐regulated expression of KV1.5, KV2.1 and KV3.4, and pulmonary vasoconstriction under hypoxia. Tension measurements on rat pulmonary artery (PA) rings, Western blots, semi‐quantitative PCR, and whole‐cell patch clamp technique were employed to investigate the effects of 15‐HETE on PKC and KV channels. Hypericin (6.8 μmol/L), a PKC inhibitor, significantly attenuated the constriction of PA rings to 15‐HETE under hypoxia. The down‐regulation of KV1.5, KV2.1 and KV3.4 channel expression, and inhibition of whole‐cell K currents (IKV) induced by 15‐HETE were rescued, and restored, respectively, by hypericin. These studies indicate that the PKC signal transduction pathway is involved in 15‐HETE‐induced rat pulmonary vasoconstriction under hypoxia. 15‐HETE suppresses the expression of KV1.5, KV2.1 and KV3.4 channels and inhibits IKV through the PKC signaling pathway in pulmonary arterial smooth muscle cells.