Skip to main content

Advertisement

Log in

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

An Erratum to this article was published on 03 September 2010

Abstract

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 ± 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO2 max). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 ± 1 μM) and G4 (14.2 ± 0.6 μM) and between G2 (20.1 ± 1.7 μM) and G4 (14.2 ± 0.6 μM). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 ± 1.2 μM) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bray MS (2000) Genomics, genes, and environmental interaction: the role of exercise. J Appl Physiol 88:788–792

    CAS  PubMed  Google Scholar 

  • Brown MD, Hogikyan RV, Dengel DR, Supiano MA (2000) Sodium-sensitive hypertension is not associated with higher sympathetic nervous system activity in older hypertensive humans. Am J Hypertens 13:873–883

    Article  CAS  PubMed  Google Scholar 

  • Campo S, Sardo AM, Campo GM, D’ascola A, Avenoso A, Castaldo M, Saitta C, Lania A, Saitta A, Calatroni A (2005) Extracellular superoxide dismutase (EC-SOD) gene mutations screening in a sample of Mediterranean population. Mutat Res 578:143–148

    CAS  PubMed  Google Scholar 

  • Cau SB, Dias-Junior CA, Montenegro MF, De Nucci G, Antunes E, Tanus-Santos JE (2008) Dose-dependent beneficial hemodynamic effects of BAY 41–2272 in a canine model of acute pulmonary thromboembolism. Eur J Pharmacol 581:132–137

    Article  CAS  PubMed  Google Scholar 

  • Channon KM, Guzik TJ (2002) Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors. J Physiol Pharmacol 53:515–524

    CAS  PubMed  Google Scholar 

  • Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42:1206–1252

    Article  CAS  PubMed  Google Scholar 

  • Cohen RA, Vanhoutte PM (1995) Endothelium-dependent hyperpolarization: beyond nitric oxide and cyclic GMP. Circulation 92:3337–3349

    CAS  PubMed  Google Scholar 

  • Darley-Usmar V, Wiseman H, Halliwell B (1995) Nitric oxide and oxygen radicals: a question of balance. FEBS Lett 369:131–135

    Article  CAS  PubMed  Google Scholar 

  • Di Massimo C, Scarpelli P, Di Lorenzo N, Caimi G, Di Orio F, Ciancarelli MG (2006) Impaired plasma nitric oxide availability and extracellular superoxide dismutase activity in healthy humans with advancing age. Life Sci 78:1163–1167

    Article  CAS  PubMed  Google Scholar 

  • Dominiczak AF, Bohr DF (1995) Nitric oxide and its putative role in hypertension. Hypertension 25:1202–1211

    CAS  PubMed  Google Scholar 

  • Doris PA (2002) Hypertension genetics, single nucleotide polymorphisms, and the common disease: common variant hypothesis. Hypertension 39:323–331

    Article  CAS  PubMed  Google Scholar 

  • Erbs S, Baither Y, Linke A, Adams V, Shu Y, Lenk K, Gielen S, Dilz R, Schuler G, Hambrecht R (2003) Promoter but not exon 7 polymorphism of endothelial nitric oxide synthase affects training-induced correction of endothelial dysfunction. Arterioscler Thromb Vasc Biol 23:1814–1819

    Article  CAS  PubMed  Google Scholar 

  • Feairheller DL, Brown MD, Park JY, Brinkley TE, Basu S, Hagberg JM, Ferrell RE, Fenty-Stewart NM (2009) Exercise training, NADPH oxidase p22phox gene polymorphisms, and hypertension. Med Sci Sports Exerc 41:1421–1428

    Article  CAS  PubMed  Google Scholar 

  • Fisher AB, Chien S, Barakat AI, Nerem RM (2001) Endothelial cellular response to altered shear stress. Am J Physiol Lung Cell Mol Physiol 281:L529–L533

    CAS  PubMed  Google Scholar 

  • Fukai T (2007) Extracellular SOD inactivation in high-volume hypertension: role of hydrogen peroxide. Arterioscler Thromb Vasc Biol 27:442–444

    Article  CAS  PubMed  Google Scholar 

  • Gladwin MT, Raat NJ, Shiva S, Dezfulian C, Hogg N, Kim-Shapiro DB, Patel RP (2006) Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am J Physiol Heart Circ Physiol 291:H2026–H2035

    Article  CAS  PubMed  Google Scholar 

  • Gomes VA, Casella-Filho A, Chagas AC, Tanus-Santos JE (2008) Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome. Nitric Oxide 19:345–350

    Article  CAS  PubMed  Google Scholar 

  • Guzik TJ, Olszanecki R, Sadowski J, Kapelak B, Rudzinski P, Jopek A, Kawczynska A, Ryszawa N, Loster J, Jawien J, Czesnikiewicz-Guzik M, Channon KM, Korbut R (2005) Superoxide dismutase activity and expression in human venous and arterial bypass graft vessels. J Physiol Pharmacol 56:313–323

    CAS  PubMed  Google Scholar 

  • Hagberg JM, Park JJ, Brown MD (2000) The role of exercise training in the treatment of hypertension: an update. Sports Med 30:193–206

    Article  CAS  PubMed  Google Scholar 

  • Heltianu C, Costache G, Gafencu A, Diaconu M, Bodeanu M, Cristea C, Azibi K, Poenaru L, Simionescu M (2005) Relationship of eNOS gene variants to diseases that have in common an endothelial cell dysfunction. J Cell Mol Med 9:135–142

    Article  CAS  PubMed  Google Scholar 

  • Higashi Y, Yoshizumi M (2004) Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacol Ther 102:87–96

    Article  CAS  PubMed  Google Scholar 

  • Higashi Y, Sasaki S, Sasaki N, Nakagawa K, Ueda T, Yoshimizu A, Kurisu S, Matsuura H, Kajiyama G, Oshima T (1999) Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension. Hypertension 33:591–597

    CAS  PubMed  Google Scholar 

  • Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377:239–242

    Article  CAS  PubMed  Google Scholar 

  • Hudlicka O, Brown MD (2009) Adaptation of skeletal muscle microvasculature to increased or decreased blood flow: role of shear stress, nitric oxide and vascular endothelial growth factor. J Vasc Res 46:504–512

    Article  CAS  PubMed  Google Scholar 

  • Jones JM, Dowling TC, Park JJ, Phares DA, Park JY, Obisesan TO, Brown MD (2007) Differential aerobic exercise-induced changes in plasma aldosterone between African Americans and Caucasians. Exp Physiol 92:871–879

    Article  CAS  PubMed  Google Scholar 

  • Kim IJ, Bae J, Lim SW, Cha DH, Cho HJ, Kim S, Yang DH, Hwang SG, Oh D, Kim NK (2007) Influence of endothelial nitric oxide synthase gene polymorphisms (−786T > C, 4a4b, 894G > T) in Korean patients with coronary artery disease. Thromb Res 119:579–585

    Article  CAS  PubMed  Google Scholar 

  • Kingwell BA (2000) Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease. Faseb J 14:1685–1696

    Article  CAS  PubMed  Google Scholar 

  • Kojda G, Hambrecht R (2005) Molecular mechanisms of vascular adaptations to exercise. Physical activity as an effective antioxidant therapy? Cardiovasc Res 67:187–197

    Article  CAS  PubMed  Google Scholar 

  • Kuru O, Senturk UK, Demir N, Yesilkaya A, Erguler G, Erkilic M (2002) Effect of exercise on blood pressure in rats with chronic NOS inhibition. Eur J Appl Physiol 87:134–140

    Article  CAS  PubMed  Google Scholar 

  • Landmesser U, Harrison DG, Drexler H (2006) Oxidant stress—a major cause of reduced endothelial nitric oxide availability in cardiovascular disease. Eur J Clin Pharmacol 62(Suppl 1):13–19

    Article  CAS  Google Scholar 

  • Lauer T, Kleinbongard P, Kelm M (2002) Indexes of NO bioavailability in human blood. News Physiol Sci 17:251–255

    CAS  PubMed  Google Scholar 

  • Lauer T, Heiss C, Balzer J, Kehmeier E, Mangold S, Leyendecker T, Rottler J, Meyer C, Merx MW, Kelm M, Rassaf T (2008) Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise. Basic Res Cardiol 103:291–297

    Article  CAS  PubMed  Google Scholar 

  • Li R, Lyn D, Lapu-Bula R, Oduwole A, Igho-Pemu P, Lankford B, Morgan J, Nkemdechi S, Liu G, Pack C, Silvestrov N, Von Deutsch DA, Song Q, Abukhalaf IK, Ofili E (2004) Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans. Am J Hypertens 17:560–567

    Article  CAS  PubMed  Google Scholar 

  • Li H, Witte K, August M, Brausch I, Godtel-Armbrust U, Habermeier A, Closs EI, Oelze M, Munzel T, Forstermann U (2006) Reversal of endothelial nitric oxide synthase uncoupling and up-regulation of endothelial nitric oxide synthase expression lowers blood pressure in hypertensive rats. J Am Coll Cardiol 47:2536–2544

    Article  CAS  PubMed  Google Scholar 

  • Lounsbury KM, Hu Q, Ziegelstein RC (2000) Calcium signaling and oxidant stress in the vasculature. Free Radic Biol Med 28:1362–1369

    Article  CAS  PubMed  Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  • Metzger IF, Souza-Costa DC, Marroni AS, Nagassaki S, Desta Z, Flockhart DA, Tanus-Santos JE (2005) Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men. Pharmacogenet Genomics 15:565–570

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Moncada S (1994) Nitric oxide. J Hypertens Suppl 12:S35–S39

    CAS  PubMed  Google Scholar 

  • Moncada S, Palmer RM, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142

    CAS  PubMed  Google Scholar 

  • Nagassaki S, Metzger IF, Souza-Costa DC, Marroni AS, Uzuelli JA, Tanus-Santos JE (2005) eNOS genotype is without effect on circulating nitrite/nitrate level in healthy male population. Thromb Res 115:375–379

    Article  CAS  PubMed  Google Scholar 

  • Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, Motoyama T, Saito Y, Ogawa Y, Miyamoto Y, Nakao K (1999) T-786–> C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 99:2864–2870

    CAS  PubMed  Google Scholar 

  • Ohta M, Nanri H, Matsushima Y, Sato Y, Ikeda M (2005) Blood pressure-lowering effects of lifestyle modification: possible involvement of nitric oxide bioavailability. Hypertens Res 28:779–786

    Article  CAS  PubMed  Google Scholar 

  • Park JY, Ferrell RE, Park JJ, Hagberg JM, Phares DA, Jones JM, Brown MD (2005) NADPH oxidase p22phox gene variants are associated with systemic oxidative stress biomarker responses to exercise training. J Appl Physiol 99:1905–1911

    Article  CAS  PubMed  Google Scholar 

  • Preti SC, Da Cunha V, Vassallo DV, Stefanon I (2005) The superoxide dismutase mimetic, tempol, reduces the bioavailability of nitric oxide and does not alter L-NAME-induced hypertension in rats. Basic Clin Pharmacol Toxicol 97:29–34

    Article  CAS  PubMed  Google Scholar 

  • Robert L (1999) Aging of the vascular-wall and atherosclerosis. Exp Gerontol 34:491–501

    Article  CAS  PubMed  Google Scholar 

  • Rossi GP, Taddei S, Virdis A, Cavallin M, Ghiadoni L, Favilla S, Versari D, Sudano I, Pessina AC, Salvetti A (2003) The T-786C and Glu298Asp polymorphisms of the endothelial nitric oxide gene affect the forearm blood flow responses of Caucasian hypertensive patients. J Am Coll Cardiol 41:938–945

    Article  CAS  PubMed  Google Scholar 

  • Rush JW, Aultman CD (2008) Vascular biology of angiotensin and the impact of physical activity. Appl Physiol Nutr Metab 33:162–172

    Article  CAS  PubMed  Google Scholar 

  • Rush JW, Denniss SG, Graham DA (2005) Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity. Can J Appl Physiol 30:442–474

    CAS  PubMed  Google Scholar 

  • Rutherford PA (2003) Genetic influences in human hypertension. J Hypertens 21:19–22

    Article  CAS  PubMed  Google Scholar 

  • Sandrim VC (2006) Influence of T-786C polymorphism on the promoter activity of eNOS. Clin Chim Acta 367:208

    Article  CAS  PubMed  Google Scholar 

  • Sandrim VC, De Syllos RW, Lisboa HR, Tres GS, Tanus-Santos JE (2007) Influence of eNOS haplotypes on the plasma nitric oxide products concentrations in hypertensive and type 2 diabetes mellitus patients. Nitric Oxide 16:348–355

    Article  CAS  PubMed  Google Scholar 

  • Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH (1994) Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 74:349–353

    CAS  PubMed  Google Scholar 

  • Silveira LR, Pereira-da-Silva L, Juel C, Hellsten Y (2003) Formation of hydrogen peroxide and nitric oxide in rat skeletal muscle cells during contractions. Free Radic Biol Med 35:455–464

    Article  CAS  PubMed  Google Scholar 

  • Tang W, Yang Y, Wang B, Xiao C (2008) Association between a G894T polymorphism of eNOS gene and essential hypertension in Hani and Yi minority groups of China. Arch Med Res 39:222–225

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Touyz RM, Schiffrin EL (2004) Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol 122:339–352

    Article  CAS  PubMed  Google Scholar 

  • Vaneckova I, Kramer HJ, Novotna J, Kazdova L, Opocensky M, Bader M, Ganten D, Cervenka L (2005) Roles of nitric oxide and oxidative stress in the regulation of blood pressure and renal function in prehypertensive Ren-2 transgenic rats. Kidney Blood Press Res 28:117–126

    Article  CAS  PubMed  Google Scholar 

  • Wang XL, Wang J (2000) Endothelial nitric oxide synthase gene sequence variations and vascular disease. Mol Genet Metab 70:241–251

    Article  CAS  PubMed  Google Scholar 

  • Webb RC (2003) Smooth muscle contraction and relaxation. Adv Physiol Educ 27:201–206

    PubMed  Google Scholar 

  • Weiss EP, Park JJ, Mckenzie JA, Park JY, Kulaputana O, Brown MD, Phares DA, Hagberg JM (2004) Plasma nitrate/nitrite response to an oral glucose load and the effect of endurance training. Metabolism 53:673–679

    Article  CAS  PubMed  Google Scholar 

  • Zalba G, San Jose G, Moreno MU, Fortuno A, Diez J (2005) NADPH oxidase-mediated oxidative stress: genetic studies of the p22(phox) gene in hypertension. Antioxid Redox Signal 7:1327–1336

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the Fundação de Amparo a Pesquisa do Estado de São Paulo, FAPESP (04/07779-4) and Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq (557967/2009-0) for the financial support.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anderson Saranz Zago.

Additional information

Communicated by Keith George.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00421-010-1618-0

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zago, A.S., Reis Silveira, L. & Kokubun, E. Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people. Eur J Appl Physiol 110, 825–832 (2010). https://doi.org/10.1007/s00421-010-1568-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-010-1568-6

Keywords

Navigation