From sodium intake restriction to nitrate supplementation: Different measures with converging mechanistic pathways?

Nutr Metab Cardiovasc Dis. 2015 Dec;25(12):1079-86. doi: 10.1016/j.numecd.2015.09.008. Epub 2015 Oct 21.


Endothelial nitric oxide synthase is at the centre of endothelial physiology producing nitric oxide which dilates blood vessels, inhibits platelet aggregation and smooth muscle cell proliferation and reduces adhesion molecule production. The laminar shear stress is a common test used usually as the flow mediated dilatation test (FMD) which is sensitive to saturated fat, sodium and potassium although with the latter ion it is possible potassium has direct effects on ion channels in the smooth muscle cell as well as the endothelial cell. High blood pressure and blood cholesterol both reduce nitric oxide production, the latter probably by increasing caveolin-1 which binds nitric oxide synthase. Saturated fat reduces nitric oxide by elevating LDL cholesterol and caveolin-1 while insulin stimulates nitric oxide synthase activity by serine phosphorylation. Polyphenols from tea, coffee and cocoa and virgin olive oil enhance FMD and eNOS activity is essential for this activity. Wine polyphenols produce mixed results and it is not clear at present that they are beneficial. Blackberries and other polyphenol-rich fruit also enhance FMD. Dietary nitrate from beetroot and green leafy vegetables is converted to nitrite by salivary microbes and then to nitric oxide and this acts directly on the smooth muscle to lower blood pressure particularly in a low oxygen environment. Dietary nitrate also improves work efficiency and improves flow mediated dilatation.

Keywords: Laminar sheer stress; NADPH oxidase; Nitric oxide; Nitric oxide synthase; Superoxide; Tetrahydrobiopterin.

Publication types

  • Review

MeSH terms

  • Animals
  • Arginine / metabolism
  • Cardiovascular System / enzymology*
  • Diet, Sodium-Restricted
  • Dietary Supplements
  • Endothelium, Vascular / metabolism*
  • Female
  • Humans
  • Male
  • Nitrates / therapeutic use*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism*
  • Rats
  • Sensitivity and Specificity
  • Signal Transduction
  • Vasoconstriction / physiology
  • Vasodilation / physiology


  • Nitrates
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase