Chronic nitrite treatment activates adenosine monophosphate-activated protein kinase-endothelial nitric oxide synthase pathway in human aortic endothelial cells

Abstract

Endothelial dysfunction, with impaired bioavailability and/or bioactivity of the vasoprotective molecule, nitric oxide, appears to be a vital step in the initiation of atherosclerosis. Several studies have shown that dietary nitrate/nitrite can have significant benefits on human cardiovascular homeostasis. Although serum nitrite concentrations can reach micromolar levels, the physiological significance of nitrate/nitrite in normal tissues has not been fully elucidated. We investigated in vitro the chronic effects of nitrate/nitrite on endothelial nitric oxide synthase (eNOS) to determine the potential vasoprotective effects of nitrate/nitrite and the underlying molecular mechanisms. Our results demonstrate the expression of phosphorylated eNOS at Ser1177 and phosphorylated adenosine monophosphate activated protein kinase (AMPK) at Thr172 in human aortic endothelial cells were increased after nitrite treatment. We suggest that nitrite stimulation may enhance eNOS activation, which is due, in part, to AMPK activation. The AMPK–eNOS activation by nitrite may be a possible molecular mechanism underlying the vascular protective effects of dietary nitrate.

Keywords

• Nitrite
• Nitrate
• 5′AMP-activated protein kinase
• Endothelial nitric oxide synthase
• Human aortic endothelial cells
• Nitric oxide