RT Journal Article SR Electronic T1 BS21 Characterisation of an in vitro model for the donation of physiological inorganic nitrate from dietary sources: pharmacokinetics and pharmacodynamics JF Heart JO Heart FD BMJ Publishing Group Ltd and British Cardiovascular Society SP A155 OP A155 DO 10.1136/heartjnl-2019-BCS.184 VO 105 IS Suppl 6 A1 Genna Logue A1 Fairoz Belary Abdul YR 2019 UL http://heart.bmj.com/content/105/Suppl_6/A155.1.abstract AB 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 7Methods 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.9Results 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.1ReferencesHalliwel B. Free Radicals and other reactive species in Disease. Encyclopedia of life Sciences 2003:1–7.Kim-Shapiro DB, Schechter AN, Gladwin MT. Unraveling the Reactions of Nitric Oxide, Nitrite, and Hemoglobin in Physiology and Therapeutics. Arteriosclerosis, Thrombosis, and Vascular Biology 2006;26:697–705.Cermak NM, Gibala MJ, vanLoon LJC. Nitrate Supplementation’s Improvement of 10-km Time-Trial Performance in Trained Cyclists. International Journal of Sport Nutrition and Exercise Metabolism 2012;22:64–71.O. Lundberg J, Carlstrom M, Larsen FL, Weitzberg. Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovascular Research 2011;89:525–532.Bundhoo SS, Anderson RA, Sagan E, Hassan N, Pinder AG, Rogers SC, et al. Direct formation of thienopyridine-derived nitrosothiols–just add nitrite! European Journal of Pharmacology 2011 November;670(2–3):534–40.Baliga RS, Milsom AB, Ghosh SS, Trinder SL, MacAllister RJ, Ahluwalia A, et al. Dietary nitrate ameliorates pulmonary hypertension: cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase. Circulation. American Heart Association 2012;125:2922–2932.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.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.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