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

Angiotensin II (Ang II) stimulation of human umbilical vein endothelial cells (HUVEC) provoked a transient increase in intracellular calcium concentration ([Ca 2+ ] i ) and induced a phosphorylation on mitogen‐activated protein kinase/extracellular signal regulated kinase (MAPK/ERK). Treatment of HUVEC with Ca 2+ ‐ATPase inhibitor thapsigargin or Ca 2+ 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 Ca 2+ 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 [Ca 2+ ] i and PKC activation.