Alkaline pH-Induced Extracellular Regulated Protein Kinase Activation in Brain Microvascular Endothelial Cells: Differential Effects of Tris and Lowered CO2

As it was previously reported that Tris-elevated pH acutely activated extracellular regulated protein kinase (ERK) in rat aorta smooth muscle cells, this study tested whether this finding could be extended to endothelial cells and, moreover, the relevance of this finding in brain microvascular endothelial cells with respect to respiratory-induced hypocapnic alkalosis. Exposure of bovine brain microvascular endothelial cells to pH 7.90 due to Tris for 15 and 30 min activated ERK twofold. In contrast, pH elevated to 7.75 and 7.90 by lowered percent CO2 failed to activate ERK (15, 30, and 60 min). These results suggest that respiratory alkalosis due to hypocapnia does not activate ERK in brain microvascular endothelial cells. The ability of Tris to activate ERK suggests a novel pathway, possibly independent of pH elevation, whereby Tris activates ERK.