Nitrite Supplementation Attenuates Vascular Stiffness Independently of Physical ExerciseKeywords
Vascular Remodeling; Nitrites; Exercise; Vascular Stiffness
Palavras-chave
Remodelação Vascular; Nitritos; Exercício Físico; Rigidez Vascular
Keywords
Vascular Remodeling; Nitrites; Exercise; Vascular Stiffness
Palavras-chave
Remodelação Vascular; Nitritos; Exercício Físico; Rigidez Vascular
Exercise training is considered one of the most efficient non-pharmacological measures for reducing blood pressure and increasing the redox state in blood vessel walls.1 Indeed, regular exercise training can cause endothelial relaxation by increasing nitric oxide (NO) levels, with or without a reduction in the amount of reactive oxygen species (ROS). Excessive production and/or accumulation of ROS can result in redox imbalance, with decreased NO bioavailability and consequent endothelial dysfunction.1,2 In this regard, reduced NO release is one of the critical factors for the development of systemic arterial hypertension.1,3
Importantly, NO is a diatomic gaseous signaling molecule that is water-soluble and can freely pass through the cell membrane. This peptide is essential in the regulation of several physiological actions in the body, being of utmost importance for vasodilation, immune response, neurotransmission, apoptosis, and genetic regulation.4 When released, NO diffuses from endothelial cells to vascular smooth muscle cells, promoting relaxation and vasodilation.5 Through this mechanism, NO can reduce vascular peripheral resistance and, consequently, decrease blood pressure. In the endogenous context, NO production results from the oxidation and cleavage of the guanidine group of L-arginine, with the release of NO and L-citrulline. Then, free NO is easily transformed into nitrite and nitrate, the current products are later recycled into NO and other forms of nitrogen oxidation, through the nitrate/nitrite/NO pathway.6
From an exogenous perspective, the NO supplying could be result from food comsumption. Despite this, 75% of the nitrate from food is excreted in the urine, and the residual is absorbed by the salivary glands, which transform nitrate into nitrite; when swallowing saliva, nitrite is protonated and converted into nitrous acid, which is also converted into NO.6 Therefore, the ingestion of foods rich in nitrate and nitrite (beets, lettuce, and spinach), or even the consumption of specific supplements, have the potential to increase the NO supplying. With continuous supplementation, there is greater bioavailability of NO, contributing to greater oxygen supply and ATP production through mitochondrial biogenesis. Consequently, there is a positive impact when it comes to improving performance in physical exercise.7
In the current issue of the Arquivos Brasileiros de Cardiologia, in Souza et al.,8 acute oral supplementation with nitrite resulted in hemodynamic benefits, such as improved stiffness and blood pressure. Indeed, arterial stiffness has been studied in different experimental models9,10 and is considered an important predictor of cardiovascular risk. In this most recent study,8 the intervention resulted in higher levels of nitrite in plasma, skeletal muscle, and heart, independently of aerobic exercise. Therefore, treatment with nitrite may be an alternative to increase its concentrations and, consequently, contribute to greater bioavailability of NO. In this context, systolic blood pressure was shown to be reduced in response to nitrite and exercise training independently, and the combination of the two interventions did not result in additional benefits. Furthermore, nitrite supplementation demonstrated benefits in cardiac remodeling and vascular relaxation.
A possible explanation for these findings is the increase in vascular endothelial growth factor, decrease in ROS concentration, increase in NO production and concentration, reduction in Ang II production, and lower sympathetic activity.11,12 Other studies have shown that oral nitrite supplementation protects the vascular endothelium from antioxidant activity, inhibiting and/or reducing the activity of NADPH oxidase and xanthine oxidoreductase in animal models.13,14 Therefore, oral nitrite supplementation, by itself, promotes multiple hemodynamic benefits, such as improved vascular stiffness, showing that, like physical exercise, it may be an alternative for the prevention and treatment of arterial hypertension.
Acknowledgments
Federal University of Mato Grosso do Sul – UFMS/MEC – Brazil, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Financial code 001.
References
-
1 Korsager ML, Matchkov VV. Hypertension and Physical Exercise: The Role of Oxidative Stress. Medicina. 2016;52(1):19-27. doi: 10.1016/j.medici.2016.01.005
» https://doi.org/10.1016/j.medici.2016.01.005 -
2 Ghisi GLM, Durieux A, Pinho R, Benetti M. Exercício Físico e Disfunção Endotelial. Arq Bras Cardiol. 2010;95(5):e130-7. doi: 10.1590/S0066-782X2010001500025.
» https://doi.org/10.1590/S0066-782X2010001500025 -
3 Virdis A, Bacca A, Colucci R, Duranti E, Fornai M, Materazzi G, et al. Endothelial Dysfunction in Small Arteries of Essential Hypertensive Patients: Role of Cyclooxygenase-2 in Oxidative Stress Generation. Hypertension. 2013;62(2):337-44. doi: 10.1161/HYPERTENSIONAHA.111.00995.
» https://doi.org/10.1161/HYPERTENSIONAHA.111.00995 -
4 Andrabi SM, Sharma NS, Karan A, Shahriar SMS, Cordon B, Ma B, et al. Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications. Adv Sci. 2023;10(30):e2303259. doi: 10.1002/advs.202303259.
» https://doi.org/10.1002/advs.202303259 -
5 Vanhoutte PM, Shimokawa H, Tang EHC, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiol. 2009;196(2):193-222. doi: 10.1111/j.1748-1716.2009.01964.x.
» https://doi.org/10.1111/j.1748-1716.2009.01964.x -
6 Oliveira-Paula GH, Pinheiro LC, Tanus-Santos JE. Mechanisms Impairing Blood Pressure Responses to Nitrite and Nitrate. Nitric Oxide. 2019;85:35-43. doi: 10.1016/j.niox.2019.01.015.
» https://doi.org/10.1016/j.niox.2019.01.015 -
7 Bryan NS, Burleigh MC, Easton C. The Oral Microbiome, Nitric Oxide and Exercise Performance. Nitric Oxide. 2022;125-126:23-30. doi: 10.1016/j.niox.2022.05.004.
» https://doi.org/10.1016/j.niox.2022.05.004 -
8 Souza TP, Tardelli LP, Nicoletti RA, Jacomini AM, Martins GFM, Pinheiro LC, et al. Short-term Oral Nitrite Administration Decreases Arterial Stiffness in Both Trained and Sedentary Wistar Rats. Arq Bras Cardiol. 2024; 121(12):e20230783. DOI: https://doi.org/10.36660/abc.20230783i
» https://doi.org/10.36660/abc.20230783i -
9 Laurent S, Boutouyrie P. Arterial Stiffness and Hypertension in the Elderly. Front Cardiovasc Med. 2020;7:544302. doi: 10.3389/fcvm.2020.544302.
» https://doi.org/10.3389/fcvm.2020.544302 -
10 Fabricio MF, Jordão MT, Miotto DS, Ruiz TFR, Vicentini CA, Lacchini S, et al. Standardization of a New Non-Invasive Device for Assessment of Arterial Stiffness in Rats: Correlation with Age-Related Arteries’ Structure. MethodsX. 2020;7:100901. doi: 10.1016/j.mex.2020.100901.
» https://doi.org/10.1016/j.mex.2020.100901 -
11 Paula SM, Fernandes T, Couto GK, Jordão MT, Oliveira EM, Michelini LC, et al. Molecular Pathways Involved in Aerobic Exercise Training Enhance Vascular Relaxation. Med Sci Sports Exerc. 2020;52(10):2117-2126. doi: 10.1249/MSS.0000000000002355.
» https://doi.org/10.1249/MSS.0000000000002355 -
12 Suvorava T, Cortese-Krott MM. Exercise-Induced Cardioprotection via eNOS: A Putative Role of Red Blood Cell Signaling. Curr Med Chem. 2018;25(34):4457-74. doi: 10.2174/0929867325666180307112557.
» https://doi.org/10.2174/0929867325666180307112557 -
13 Amaral JH, Ferreira GC, Pinheiro LC, Montenegro MF, Tanus-Santos JE. Consistent Antioxidant and Antihypertensive Effects of Oral Sodium Nitrite in DOCA-Salt Hypertension. Redox Biol. 2015;5:340-6. doi: 10.1016/j.redox.2015.06.009.
» https://doi.org/10.1016/j.redox.2015.06.009 -
14 Gao X, Yang T, Liu M, Peleli M, Zollbrecht C, Weitzberg E, et al. NADPH Oxidase in the Renal Microvasculature is a Primary Target For Blood Pressure-Lowering Effects by Inorganic Nitrate and Nitrite. Hypertension. 2015;65(1):161-70. doi: 10.1161/HYPERTENSIONAHA.114.04222.
» https://doi.org/10.1161/HYPERTENSIONAHA.114.04222
