Angiotensin II effect on calcium mobilization and mitogen‐activated protein kinase activation in human umbilical vein endothelial cells

Abstract

AbstractAngiotensin II (Ang II) stimulation of human umbilical vein endothelial cells (HUVEC) provoked a transient increase in intracellular calcium concentration ([Ca2+]i) and induced a phosphorylation on mitogen‐activated protein kinase/extracellular signal regulated kinase (MAPK/ERK). Treatment of HUVEC with Ca2+‐ATPase inhibitor thapsigargin or Ca2+ ionophore A23187 resulted in a significant increase in ERK1/2 phosphorylation. Ang II‐stimulated ERK1/2 phosphorylation was sensitive to the pretreatment of cells with U73122, a selective phospholipase C (PLC) inhibitor, resulting in a pronounced decrease of ERK1/2 phosphorylation. Additionally, Ang II‐induced ERK1/2 phosphorylation was prominently reduced by the removal of Ca2+ from extracellular medium. Furthermore, activation of ERK1/2 was mimicked by phorbol 12‐myristate acetate, a protein kinase C (PKC) activator, while the Ang II‐provoked ERK1/2 phosphorylation was markedly attenuated by a PKC inhibition after the treatment of HUVEC with GFX109203X, a specific PKC inhibitor. This study demonstrated that Ang II mediates an increase in the MAPK/ERK phosphorylation in HUVEC which is dependent on [Ca2+]i and PKC activation.