Direct Evidence that Protein Kinase C Mediates the Acute Inhibitory Effect of Oxidised Low Density Lipoprotein on Acetylcholine-induced Endothelium-dependent Relaxation of Rabbit Aorta

This study further examines the involvement of protein kinase C and superoxide anions in the inhibition of agonist-induced endothelium-dependent relaxation by oxidised low density lipoprotein (LDL). Pretreatment of rabbit aorta rings with either oxidised low density lipoprotein or phorbol dibutyrate (PDB) inhibited acetylcholine-induced endothelium-dependent relaxation, but not endothelium-independent relaxations to glyceryl trinitrate. Prior exposure of the rings to either of the specific protein kinase C inhibitors Ro 31-8220 or Ro 31-7549 prevented or reduced respectively the inhibition of acetylcholine-induced relaxation by oxidised LDL or PDB. Neither inhibitor alone affected acetylcholine-induced relaxation. We directly demonstrate for the first time that oxidised, but not native, LDL produces a prolonged activation of protein kinase C in endothelial cells, which was prevented by pretreatment with Ro 31-8220. Oxidised or native LDL, or Ro 31-8220 increased superoxide anion production by rabbit aorta...