Dietary Salt Activates An Endothelial Pyk2/c-Src/PI3-Kinase Complex To Promote Endothelial NO Synthase Phosphorylation

摘要

While many laboratories have shown that dietary NaCl (salt) intake increases nitric oxide (NO) production in rodents and humans, the mechanism has not been uncovered. In the present study, pharmacological and dominant-negative strategies were used to show that feeding a formulated diet containing increased amounts of salt to young male Sprague-Dawley rats induced the formation of an endothelial cell-signaling complex that contained proline-rich tyrosine kinase 2 (Pyk2), c-Src (also known as pp60^c-src) and phosphatidylinositol 3-kinase (PI3-kinase). In the setting of a high-salt diet, Pyk2 served as the scaffold for c-Src-mediated PI3-kinase activation. PI3-kinase was the upstream activator of protein kinase B (Akt), which was responsible for phosphorylation of the rat endothelial isoform of nitric oxide synthase (NOS3) at S1176 and thereby promoted the increase in NO production. The combined findings illustrated the crucial role for a Pyk2-signaling complex in the endothelial response to salt intake.