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Synergistic Effects of Light Therapy and Nutrition • Certain vegetables possess a high nitrate content representing a potential source of vasoprotective nitric oxide via bioactivation. • In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantiallyreduced(max 10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. Nitric Oxide, Oxidative Stress Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite Andrew J. Webb, Nakul Patel, Stavros Loukogeorgakis, Mike Okorie, Zainab Aboud, Shivani Misra, Rahim Rashid, Philip Miall, John Deanfield, Nigel Benjamin, Raymond MacAllister, Adrian J. Hobbs, Amrita Ahluwalia Abstract—Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (max 10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a “natural” low cost approach for the treatment of cardiovascular disease. (Hypertension. 2008;51:784-790.) Key Words: diet nitric oxide blood pressure hypertension ischemia/reperfusion platelets endothelium Perhaps the largest public health initiative in the Western world has focused on improvement of diet, particularly in those with a high risk of cardiovascular disease. Trials have shown that diets rich in fruits and vegetables reduce blood pressure (BP; Dietary Approaches to Stop Hypertension; DASH, Vegetarian Diet and BP)1,2 and adverse cardiovascu- lar events.3–7 These protective effects have previously been attributed to the high antioxidant vitamin content, yet large clinical trials have failed to provide evidence in support of this thesis.8,9 The greatest protection against coronary heart disease afforded by a change in diet is that associated with the consumption of green leafy vegetables (eg, spinach, lettuce).6 Such vegetables, also including beetroot, commonly have a high inorganic nitrate (NO3) content.10,11 In humans, after absorption through the stomach wall, 25% of consumed nitrate enters the enterosalivary circulation where it is re- duced to nitrite (NO2) by bacterial nitrate reductases from facultative anaerobes on the dorsal surface of the tongue.12–14 This nitrite is swallowed and in the acidic environment of the stomach is reduced to nitric oxide (NO) or re-enters the circulation as nitrite. Indeed, it has been hypothesized that dietary nitrate represents an intravascular source of the pleiotropic, vasoprotective molecule NO, which supplements conventional NO generation by NO synthases (NOS).15 Endothelium-derived NO is a potent dilator, governs sys- temic BP, and retards atherogenesis (NO inhibits inflamma- tory cell recruitment and platelet aggregation).16 Conse- quently, numerous cardiovascular pathologies (including preh ypertension,17 hypertension,18 atherosclerosis,19 and stroke20) are associated with endothelial dysfunction and diminished NO bioactivity. Recently, studies have demonstrated that nitrite confers marked protection against ischemia/reperfu- sion (I/R) injury in the myocardial, hepatic, renal, pulmonary, and cerebral vasculature.21,22 This cytoprotective effect has been attributed to reduction of nitrite to NO during ischemia or hypoxemia (conditions that inactivate endothelial NOS, the Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. Received October 16, 2007; first decision November 10, 2007; revision accepted January 11, 2008. From Clinical Pharmacology (A.J.W., N.P., Z.A., S.M., R.R., A.A.), William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University, London, UK; Clinical Pharmacology (S.L., M.O., R.M.), The Rayne Institute, University College London, UK; Clinical Biochemistry (P.M.), William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, London, UK; the Institute of Child Health (J.D.), University College London, UK; Peninsula Medical School (N.B.), Tamar Science Park, Plymouth UK; and the Wolfson Institute for Biomedical Research (A.J.H.), University College London, UK. Correspondence to Professor Amrita Ahluwalia, Clinical Pharmacology, William Harvey Research Institute, Barts & the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. E-mail a.ahluwalia@qmul.ac.uk © 2008 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.107.103523 Downloaded from http://hyper.ahaj7o8u4rnals.org/ by guest on July 19, 2015PDF Image | Synergistic Effects of Light Therapy and Nutrition
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