Abstract
Background & Objectives: Nitric Oxide (NO) is frequently produced by the enzyme nitric oxide synthase (NOS) and is crucial for the control and effectiveness of the cardiovascular system. However, there is a substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular obstacles. Fortunately, NO can also be produced by sequential reduction of inorganic nitrates supplementation. This proves that NO from inorganic nitrate supplements can compensate for inadequate NOS activity, thus providing cardio protective benefits.
Discussion: This review focuses on the general information about nitrous oxide, its types and mechanism of action and the fact that overview of inadequate NOS activity for cardio protective benefits was often studied for cardiovascular treatments.
Conclusion: We concluded that the natural plant NO is essential for cardiovascular activity to target site with desired concentration. Moreover, the researchers focused on evidence that suggested that nitrate supplementation could help regulate blood pressure, limit progression of atherosclerosis, and improve myocardial contractility in both healthy individuals and those with cardiovascular diseases.
Keywords: Nitric oxide, nitric oxide synthase, nitrate, nitrite, cardiovascular disease no., NOS.
Graphical Abstract
[1]
John, L.I. Inorganic nitrate supplements for cardiovascular Health. Meth. Deb. Cardio. J., 2019, 15(3), 200-206.
[2]
Forstermann, U.; Sessa, W.C. Nitric oxide synthase: Regulation and function. Eur Heart J., 2017, 33(7), 829-832.
[3]
Lundberg, J.O.; Weitzberg, E.; Gladwin, M.T. The nitrate-nitrile-nitric oxide pathway in physiology and therapeutics. Nat. Rav. Drug Disc., 2008, 1(2), 156-167.
[http://dx.doi.org/10.1038/nrd2466]
[http://dx.doi.org/10.1038/nrd2466]
[4]
Taddei, S.; Virdis, A.; Ghaidoni, L. Age-related reduction of NO availability and oxidative stress in humans. Hypertension, 2001, 38(2), 274-279.
[http://dx.doi.org/10.1161/01.HYP.38.2.274]
[http://dx.doi.org/10.1161/01.HYP.38.2.274]
[5]
Martin, M.J.; Jimenez, M.V. New issues about nitric oxide and its effects on the gastrointestinal tract. Curr. Pharm. Des., 2001, 7(10), 881-908.
[http://dx.doi.org/10.2174/1381612013397645]
[http://dx.doi.org/10.2174/1381612013397645]
[6]
Lidder, S.; Webb, A.J. Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway. Br. J. Clin. Pharmcol., 2012, 75(3), 677-697.
[7]
Kevil, C.G.; Kolluru, G.K.; Pattillo, C.B.; Giordano, T. Inorganic nitrite therapy: Historical perspective and future directions. Free Radical Biol. Med., 2011, 51(3), 565-794.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.042]
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.042]
[8]
Rees, D.D.; Palmer, R.M.J.; Moncada, S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc. Natl. Acad Sci. USA, 1989, 86(9), 3375-3378.
[http://dx.doi.org/10.1073/pnas.86.9.3375]
[http://dx.doi.org/10.1073/pnas.86.9.3375]
[9]
Vallance, P.; Collier, J.; Moncada, S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet, 1989, 334(8670), 997-1000.
[http://dx.doi.org/10.1016/S0140-6736(89)91013-1]
[http://dx.doi.org/10.1016/S0140-6736(89)91013-1]
[10]
Webb, A.J.; Patel, N.; Loukogeorgakis, S. Acute blood pressure lowering, vasoprotective and anti-platelet properties of dietary nitrate via bioconversion to nitrite. Hypertension, 2008, 51(3), 784-790.
[11]
Vanhatalo, A.; Bailey, S.J.; Blackwell, J.R. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am. J. Physiol Regul. Integr. Comp. Physiol., 2010, 299(4), 1121-1131.
[http://dx.doi.org/10.1152/ajpregu.00206.2010]
[http://dx.doi.org/10.1152/ajpregu.00206.2010]
[12]
Lansley, K.E.; Winyard, P.G.; Fulford, J. Dietary nitrate supplementation reduces the O2 cost of walking and running: A placebo-controlled study. J. Appl. Physiol., 2011, 110(3), 591-600.
[13]
Wylie, L.J.; Kelly, J.; Bailey, S.J. Beet juice and exercise: Pharmacodynamics and dose-response relationships. J. Appl. Physiol., 2013, 115(3), 325-336.
[14]
Kenjale, A.A.; Ham, K.L.; Stabler, T. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J. Appl. Physiol., 2011, 110(6), 1582-1591.
[15]
Ghosh, S.M.; Kapil, V.; Fuentes-Calvo, Enhanced vasodilator activity of nitrite in hypertension: Critical role for erythrocytic xanthine oxidoreductase and translational potential. Hypertension, 2013, 61(5), 1091-1102.
[16]
Hobbs, D. A.; George, T.W.; Lovegrove, J.A. The effects of dietary nitrate on blood pressure and endothelial function: A review of human intervention studies. Nut Res. Rev., 2013, 26(2), 210-222.
[http://dx.doi.org/10.1017/S0954422413000188]
[http://dx.doi.org/10.1017/S0954422413000188]
[17]
Lara, J.; Ashor, A.W.; Oggioni, C.; Ahluwalia, A.; Mathers, J.C.; Siervo, M. Effects of inorganic nitrate and beetroot supplementation on endothelial function: A systematic review and meta-analysis. Eur. J. Nutr., 2016, 55(2), 451-459.
[http://dx.doi.org/10.1007/s00394-015-0872-7]
[http://dx.doi.org/10.1007/s00394-015-0872-7]
[18]
Machha, A.; Schechter, A.N. Dietary nitrite and nitrate: A review of potential mechanisms of cardiovascular benefits. Eur. J. Nutr., 2011, 50(5), 293-303.
[http://dx.doi.org/10.1007/s00394-011-0192-5]
[http://dx.doi.org/10.1007/s00394-011-0192-5]
[19]
Richardson, G.; Hicks, S.L.; O’Byrne, S. The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans. Nitric Oxide, 2002, 7(1), 24-29.
[20]
Velmurugan, S.; Kapil, V.; Ghosh, S.M.; Davies, S.; McKnight, A.; Aboud, Z.; Khambata, R.S.; Webb, A.J.; Poole, A.; Ahluwalia, A. Antiplatelet effects of dietary nitrate in healthy volunteers: Involvement of cGMP and influence of sex. Free Radic. Biol. Med., 2013, 65, 1521-1532.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.06.031] [PMID: 23806384]
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.06.031] [PMID: 23806384]
[21]
Apostoli, G.L.; Solomon, A.; Smallwood, M.J. Role of inorganic nitrate and nitrite in driving nitric oxide-cGMP-mediated inhibition of platelet aggregation in vitro and in vivo. J. Thromb. Haemost., 2014, 12(11), 1880-1889.
[22]
Totani, L.; Evangelista, V. Platelet-leukocyte interactions in cardiovascular disease and beyond. Arterioscler Thromb Vasc Biol., 2010, 30(12), 2357-2361.
[http://dx.doi.org/10.1161/ATVBAHA.110.207480]
[http://dx.doi.org/10.1161/ATVBAHA.110.207480]
[23]
Rosenfeld, M.E. Cellular mechanisms in the development of atherosclerosis. Diabetes Res. Clin. Pract., 1996, 30(1), S1-S11.
[24]
Kubes, P.; Suzuki, M.; Granger, D.N. Nitric oxide: An endogenous modulator of leukocyte adhesion. Proc. Natl. Acad. Sci. USA, 1991, 88(11), 4651-4655.
[25]
Hayakawa, H.; Raij, L. Relationship between hypercholesterolaemia, endothelial dysfunction and hypertension. J. Hypertens., 1999, 17(5), 611-619.
[26]
Stokes, K.Y.; Dugas, T.R.; Tang, Y.; Garg, H.; Guidry, E.; Bryan, N.S. Dietary nitrite prevents hypercholesterolemia microvascular inflammation and reverses endothelial dysfunction. Am. J. Physiol. Heart Circ. Physiol., 2009, 296(5), 281-288.
[27]
Jädert, C.; Petersson, J.; Massena, S. Decreased leukocyte recruitment by inorganic nitrate and nitrite in microvascular inflammation and NSAID-induced intestinal injury. Free Radic. Biol. Med., 2012, 52(3), 683-692.
[28]
Garg, U.C.; Hassid, A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J. Clin. Invest., 1989, 83(5), 1774-1777.
[29]
Sarkar, R.; Meinberg, E.G.; Stanley, J.C.; Gordon, D.; Webb, R.C. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. Circ. Res., 1996, 78(2), 225-230.
[http://dx.doi.org/10.1161/01.RES.78.2.225]
[http://dx.doi.org/10.1161/01.RES.78.2.225]
[30]
Alef, M.J.; Vallabhaneni, R.; Carchman, E. Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats. J. Clin. Invest., 2011, 121(4), 1646-1656.
[31]
Hermández, A.; Schiffer, T.A.; Ivarsson, N. Dietary nitrate increases tetanic [Ca2+]I and contractile force in mouse fast-twitch muscle. J. Physiol., 2001, 590(15), 3575-3583.
[32]
Haider, G.; Folland, J.P. Nitrate supplementation enhances the contractile properties of human skeletal muscle. Med. Sci. Sports Exerc., 2014, 48(12), 2234-2243.
[http://dx.doi.org/10.1249/MSS.0000000000000351]
[http://dx.doi.org/10.1249/MSS.0000000000000351]
[33]
Coggan, A.R.; Leibowitz, J.L.; Kadkhodayan, A.; Thomas, D.P.; Ramamurthy, S.; Spearie, C.A.; Waller, S.; Farmer, M.; Peterson, L.R. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide, 2015, 48, 16-21.
[http://dx.doi.org/10.1016/j.niox.2014.08.014] [PMID: 25199856]
[http://dx.doi.org/10.1016/j.niox.2014.08.014] [PMID: 25199856]
[34]
Coggan, A.R.; Leibowitz, J.L.; Spearie, C.A. Acute dietary nitrate intake improves muscle contractile function in patients with heart failure: A double-blind, placebo-controlled, randomized trial. Circ. Heart Fail., 2015, 8(5), 914-920.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002141]
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.115.002141]
[35]
Pironti, G.; Ivarsson, N.; Yang, J. Dietary nitrate improves cardiac contractility via enhanced cellular Ca2+ signaling. Basic Res. Cardiol., 2016, 111(3), 34-47.
[36]
Zamani, P.; Rawat, D.; Shiva-Kumar, P. Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction. Circulation, 2015, 131(4), 371-380.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012957]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.012957]
[37]
Borlaug, B.A.; Koepp, K.E.; Melenovsky, V. Sodium nitrite improves exercise hemodynamics and ventricular performance in heart failure with preserved ejection fraction. J. Am. Coll. Cardiol., 2015, 66(15), 1672-1682.
[38]
D’El-Rei, J.; Cunha, A.R.; Trindade, M.; Neves, M.F. Beneficial effects of dietary nitrate on endothelial function and blood pressure levels. 2016, 2016, 6.
[http://dx.doi.org/10.1155/2016/6791519]
[http://dx.doi.org/10.1155/2016/6791519]
[39]
Ivy, J.L. Inorganic nitrate supplementation for cardiovascular health. Methodist DeBakey Cardiovasc. J., 2019, 15(3), 200-206.
[http://dx.doi.org/10.14797/mdcj-15-3-200] [PMID: 31687099]
[http://dx.doi.org/10.14797/mdcj-15-3-200] [PMID: 31687099]
[40]
Machha, A.; Schechter, A.N. Inorganic nitrate: A major player in the cardiovascular health benefits of vegetables? Nutr. Rev., 2012, 70(6), 367-372.
[http://dx.doi.org/10.1111/j.1753-4887.2012.00477] [PMID: 22646129]
[http://dx.doi.org/10.1111/j.1753-4887.2012.00477] [PMID: 22646129]
[41]
Machha, A.; Schechter, A.N. Inorganic nitrate: A major player in the cardiovascular health benefits of vegetables? Nutr. Rev., 2012, 70(6), 367-372.
[http://dx.doi.org/10.1111/j.1753-4887.2012.00477.x] [PMID: 22646129]
[http://dx.doi.org/10.1111/j.1753-4887.2012.00477.x] [PMID: 22646129]
[42]
Jansson, E.A.; Huang, L.; Malkey, R.; Govoni, M.; Nihlén, C.; Olsson, A.; Stensdotter, M.; Petersson, J.; Holm, L.; Weitzberg, E.; Lundberg, J.O. A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis. Nat. Chem. Biol., 2008, 4(7), 411-417.
[http://dx.doi.org/10.1038/nchembio.92] [PMID: 18516050]
[http://dx.doi.org/10.1038/nchembio.92] [PMID: 18516050]
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