Salt inactivates endothelial nitric oxide synthase in endothelial cells

Area of Science:

• Cardiovascular Physiology
• Endothelial Cell Biology
• Hypertension Research

Background:

• Elevated plasma sodium concentrations (1-4 mmol/L) are observed in individuals with high salt intake and essential hypertension.
• The direct impact of these small sodium concentration increases on endothelial nitric oxide synthase (eNOS) function and hypertension development requires elucidation.

Purpose of the Study:

• To investigate whether physiological increases in sodium concentration directly alter endothelial nitric oxide synthase (eNOS) function.
• To determine if impaired eNOS function contributes to the development of hypertension.

Main Methods:

• Assessed NOS activity in living bovine aortic endothelial cells and Chinese hamster ovary cells expressing eNOS using three independent assays.
• Utilized an ex vivo aortic angiogenesis assay to evaluate salt's effect on nitric oxide (NO)-dependent endothelial cell proliferation.
• Monitored in vivo blood pressure changes following salt infusion in animal models.

Main Results:

• A 5-mmol/L increase in salt concentration reduced NOS activity by 25% in a concentration-dependent manner.
• Salt exposure significantly attenuated NO-dependent endothelial cell proliferation.
• In vivo salt infusion acutely increased blood pressure in a concentration-dependent manner, confirming a link between salt, NO, and blood pressure regulation.

Conclusions:

• Endothelial nitric oxide synthase (eNOS) is sensitive to physiological changes in salt concentration.
• A 5-mmol/L rise in salt, within the range seen in hypertension, significantly suppresses eNOS activity.
• Salt-induced reduction in endothelial NO generation may be a key factor in the pathogenesis of hypertension.