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

The aim of the present study was to investigate the roles of protein kinase C (PKC) signal transduction pathway in the 15-hydroxyeicosatetraenoic acid (15-HETE)-induced down-regulation expression of K(V) 1.5, K(V) 2.1 and K(V) 3.4, 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 K(V) channels. Hypericin (6.8 micromol/L), a PKC inhibitor, significantly attenuated the constriction of PA rings to 15-HETE under hypoxia. The down-regulation of K(V) 1.5, K(V) 2.1 and K(V) 3.4 channel expression and inhibition of whole-cell K currents (I(K)(V)) 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 K(V) 1.5, K(V) 2.1 and K(V) 3.4 channels and inhibits I(K)(V) through the PKC signaling pathway in pulmonary arterial smooth muscle cells.