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Differential effect of beetroot bread on postprandial DBP according to Glu298Asp polymorphism in the eNOS gene: a pilot study

Journal of Human Hypertension volume 28, pages 726–730 (2014) Cite this article

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Abstract

Our objective was to investigate whether the presence of Glu298Asp polymorphism in the endothelial NO synthase (eNOS) gene differentially affects the postprandial blood pressure response to dietary nitrate-rich beetroot bread. A randomised, single-blind, controlled, crossover acute pilot study was performed in 14 healthy men (mean age: 34±9 years) who were retrospectively genotyped for Glu298Asp polymorphism (7GG; T carriers 7). Volunteers were randomised to receive 200 g beetroot-enriched bread (1.1 mmol nitrate) or control bread (no beetroot; 0.01 mmol nitrate) on two separate occasions 10 days apart. Baseline and incremental area under the curve of blood pressure and NOx (nitrate/nitrite) were measured for a 6-h postprandial period. A treatment × genotype interaction was observed for diastolic blood pressure (P<0.02), which was significantly lower in T carriers (P<0.01) after consumption of beetroot bread compared with control bread. No significant differences were observed in the GG group. The beneficial diastolic blood pressure reduction was observed only in the T carriers of the Glu298Asp polymorphism in the eNOS gene after consumption of nitrate-rich beetroot bread. These data require confirmation in a larger population group.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F et al. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension 2010; 56: 274–281.

    Article  CAS  Google Scholar 

  3. Larsen F, Ekblom B, Sahlin K, Lundberg J, Weitzberg E . Effects of dietary nitrate on blood pressure in healthy volunteers. New Engl J Med 1996; 26: 355.

    Google Scholar 

  4. Velmurugan S, Kapil V, Ghosh SM, Davies S, McKnight A, Aboud Z et al. Antiplatelet effects of dietary nitrate in healthy volunteers: Involvement of cGMP and influence of sex. Free Radic Biol Med 2013; 65: 1521–1532.

    Article  CAS  PubMed  Google Scholar 

  5. Bondonno CP, Yang X, Croft KD, Considine MJ, Ward NC, Rich L et al. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial. Free Radic Biol Med 2012; 52: 95–102.

    Article  CAS  Google Scholar 

  6. Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B . Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxford, UK) 2007; 191: 59–66.

    Article  CAS  Google Scholar 

  7. Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, DiMenna FJ, Wilkerson DP et al. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol 2009; 107: 1144–1155.

    Article  CAS  Google Scholar 

  8. Li H, Cui H, Kundu TK, Alzawahra W, Zweier JL . Nitric oxide production from nitrite occurs primarily in tissues not in the blood. J Biol Chem 2008; 283: 17855–17863.

    Article  CAS  PubMed  Google Scholar 

  9. Cosby K, Partovi K, Crawford J, Patel R, Reiter C, Martyr S et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 2003; 9: 1498–1505.

    Article  CAS  Google Scholar 

  10. Webb AJ, Milsom AB, Rathod KS, Chu WL, Qureshi S, Lovell MJ et al. Mechanisms underlying erythrocyte and endothelial nitrite reduction to nitric oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide synthase. Circ Res 2008; 103: 957–964.

    Article  CAS  PubMed  Google Scholar 

  11. Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol 2005; 1: 290–297.

    Article  CAS  Google Scholar 

  12. Hobbs DA, Kaffa N, George TW, Methven L, Lovegrove JA . Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched bread products in normotensive male subjects. Br J Nutr 2012; 108: 2066–2074.

    Article  CAS  Google Scholar 

  13. Hobbs DA, Goulding MG, Nguyen A, Malaver T, Walker CF, George TW et al. Acute ingestion of beetroot bread increases endothelium-independent vasodilation and lowers diastolic blood pressure in healthy men: a randomized controlled trial. J Nutr 2013; 143: 1399–1405.

    Article  CAS  Google Scholar 

  14. Hingorani AD, Liang CF, Fatibene J, Lyon A, Monteith S, Parsons A et al. A common variant of the endothelial nitric oxide synthase (Glu298—&gt;Asp) is a major risk factor for coronary artery disease in the UK. Circulation 1999; 100: 1515–1520.

    Article  CAS  Google Scholar 

  15. Tian GX, Zeng XT, Wang XB, Zhang L, Zhang W, Wei WL . Association between the endothelial nitric oxide synthase gene Glu298Asp polymorphism and coronary heart disease: a metaanalysis of 39 case–control studies. Mol Med Rep 2013; 7: 1310–1318.

    Article  CAS  Google Scholar 

  16. Metzger IF, Ishizawa MH, Rios-Santos F, Carvalho WA, Tanus-Santos JE . Endothelial nitric oxide synthase gene haplotypes affect nitrite levels in black subjects. Pharmacogenom J 2011; 11: 393–399.

    Article  CAS  Google Scholar 

  17. Metzger IF, Sertorio JT, Tanus-Santos JE . Modulation of nitric oxide formation by endothelial nitric oxide synthase gene haplotypes. Free Radic Biol Med 2007; 43: 987–992.

    Article  CAS  PubMed  Google Scholar 

  18. Metzger IF, Souza-Costa DC, Marroni AS, Nagassaki S, Desta Z, Flockhart DA et al. Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men. Pharmacogenet Genom 2005; 15: 565–570.

    Article  CAS  Google Scholar 

  19. Wang CJ, Zhao JB, Xu JL, Xiang ZL, Liang CW, Li J . Meta-analysis on the association of G894T polymorphism in endothelial nitric oxide synthase gene and essential hypertension in Chinese population. Zhonghua liu xing bing xue za zhi=Zhonghua liuxingbingxue zazhi 2009; 30: 845–849.

    PubMed  Google Scholar 

  20. Ignarro LJ, Fukuto JM, Griscavage JM, Rogers NE, Byrns RE . Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci USA 1993; 90: 8103–8107.

    Article  CAS  Google Scholar 

  21. Mikula I, Durocher S, Martasek P, Mutus B, Slama-Schwok A . Isoform-specific differences in the nitrite reductase activity of nitric oxide synthases under hypoxia. Biochem J 2009; 418: 673–682.

    Article  CAS  Google Scholar 

  22. Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 2003; 9: 1498–1505.

    Article  CAS  Google Scholar 

  23. Huang Z, Shiva S, Kim-Shapiro DB, Patel RP, Ringwood LA, Irby CE et al. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest 2005; 115: 2099–2107.

    Article  CAS  PubMed  Google Scholar 

  24. Gladwin MT, Kim-Shapiro DB . The functional nitrite reductase activity of the heme-globins. Blood 2008; 112: 2636–2647.

    Article  CAS  PubMed  Google Scholar 

  25. Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, MacArthur PH et al. Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res 2007; 100: 654–661.

    Article  CAS  Google Scholar 

  26. Tanus-Santos JE, Desai M, Flockhart DA . Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. Pharmacogenetics 2001; 11: 719–725.

    Article  CAS  Google Scholar 

  27. Silva PS, Fontana V, Luizon MR, Lacchini R, Silva WA Jr, Biagi C et al. eNOS and BDKRB2 genotypes affect the antihypertensive responses to enalapril. Eur J Clin Pharmacol 2013; 69: 167–177.

    Article  CAS  Google Scholar 

  28. Nagassaki S, Sertorio JT, Metzger IF, Bem AF, Rocha JB, Tanus-Santos JE . eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood nitrite. Free Radic Biol Med 2006; 41: 1044–1049.

    Article  CAS  PubMed  Google Scholar 

  29. Muniz JJ, Lacchini R, Rinaldi TO, Nobre YT, Cologna AJ, Martins AC et al. Endothelial nitric oxide synthase genotypes and haplotypes modify the responses to sildenafil in patients with erectile dysfunction. Pharmacogenom J 2013; 13: 189–196.

    Article  CAS  Google Scholar 

  30. Montenegro MF, Amaral JH, Pinheiro LC, Sakamoto EK, Ferreira GC, Reis RI et al. Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension. Free Radic Biol Med 2011; 51: 144–152.

    Article  CAS  Google Scholar 

  31. Pinheiro LC, Montenegro MF, Amaral JH, Ferreira GC, Oliveira AM, Tanus-Santos JE . Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats. Free Radic Biol Med 2012; 53: 701–709.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Rada Mihaylova and Dr Kim Jackson for help with cannulation during study days. The study was supported by the Reading Endowment Trust Fund and Eccentricities Ltd who supplied the intervention breads.

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Authors and Affiliations

  1. Department of Food and Nutritional Sciences, Hugh Sinclair Unit of Human Nutrition, University of Reading, Whiteknights, Reading, Berkshire, UK

    D A Hobbs & J A Lovegrove

  2. Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Whiteknights, Reading, Berkshire, UK

    D A Hobbs & J A Lovegrove

  3. Eccentricities Ltd, Camberley, Surrey, UK

    T W George

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  1. D A Hobbs
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  2. T W George
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  3. J A Lovegrove
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Correspondence to J A Lovegrove.

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Competing interests

The authors declare no conflict of interest. TWG is the managing director of Eccentricities Ltd and supplied the breads for the intervention study.

Additional information

This work was presented at the Nutrition Society Summer Meeting at Newcastle University, UK in July 2013.

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Hobbs, D., George, T. & Lovegrove, J. Differential effect of beetroot bread on postprandial DBP according to Glu298Asp polymorphism in the eNOS gene: a pilot study. J Hum Hypertens 28, 726–730 (2014). https://doi.org/10.1038/jhh.2014.16

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