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BS21 Characterisation of an in vitro model for the donation of physiological inorganic nitrate from dietary sources: pharmacokinetics and pharmacodynamics
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  1. Genna Logue1,
  2. Fairoz Belary Abdul2
  1. 1Wales Heart Research Institute
  2. 2University Hospital of Wales

Abstract

Background Nitric oxide (NO) has anti-platelet activity.1 Nitrate, nitrite and nitrosthiols (SNO) are NO intermediates.2 Exogenous NO sources include dietary inorganic nitrate and commercial products, Beet It (BI) juice and SIS® Go+ nitrate (SGN) gel.3 In the entero-salivary circulation nitrate reduces to nitrite via nitrate reductase (NR) from commensal oral bacteria.4 Nitrite reacts with gastric proteins to form R-SNO; clopidogrel may enhance production.5 Patients with coronary artery disease (CAD) have impaired endogenous NO generation.6 7

Methods A model was created enabling in vitro sodium nitrate salt (SNS) reduction by NR from Aspergillus niger.8 SGN gel, placebo gel and BI were tested using this. Product was added to gastric medium to form R-SNO, with and without clopidogrel.5 NO metabolites were quantified using ozone-based chemiluminescence.9

Results SGN gel and BI produced limited nitrite. Placebo gel (nitrate deficient) mixed with SNS also produced limited nitrite. Gel dilution improved yield. R-SNO production was greater from nitrite converted from SGN gel than SNS; clopidogrel did not enhance yield.

Key messages A model was established for the reduction of nitrate from commercial agents. R-SNO formed in gastric medium in the presence of nitrite. This helps understand a clinical study assessing therapeutic effects of nitrate on platelet activity in CAD.1

References

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  7. Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, et al. Nitric oxide, Oxidative stress. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension. American Heart Association 2008;51:784–790.

  8. Milsom AB. An assessment of Nitric Oxide metabolism in blood: a physiological role for Nitric Oxide metabolites and the implications for diabetes mellitus [PhD thesis]. Cardiff: Cardiff University; 2003.

  9. Burnley-Hall N, Abdul F, Androshchuk V, Morris K, Ossei-Gerning N, Anderson R, Rees A, James P. Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study. Thrombosis and Haemostasis 2018;118:112–122.

Conflict of interest None

  • Platelet
  • Dietary
  • Nitrate

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