Women with TT genotype for eNOS gene are more responsive in lowering blood pressure in response to exercise

Abstract

Introduction

The aim of this study was to investigate whether −786T>C endothelial nitric oxide synthase (eNOS) gene polymorphism might influence the effect of long-term exercise training (ET) on the blood pressure and its relationship with NO production in healthy postmenopausal women.

Design

Longitudinal study.

Method

Fifty-five postmenopausal women were studied in a double-blinded design. ET was performed for 3 days a week, each session consisting of 60 min during 6 months, in an intensity of 50–70% VO_2max. After that, eNOS genotype analysis was performed and women were divided into two groups: TC + CC (n = 41) and TT (n = 14) genotype.

Results

No changes were found in the anthropometric parameters after ET in both the groups. Systolic and diastolic BP values were significantly reduced in both the groups, but women with TT genotype were more responsive in lowering BP as compared with those with TC + CC genotype. Plasma nitrite/nitrate concentrations were similar at baseline in both the groups, but the magnitude of increment in NO production in response to ET was higher in women with TT genotype as compared with those with TC + CC genotype.

Conclusion

Our study shows clearly that women with or without eNOS gene polymorphism had no differences in NO production at basal conditions, but when physical exercise is applied an evident difference is detected showing that the presence of −786T>C eNOS gene polymorphism had a significant impact in the health-promoting effect of aerobic physical training on the blood pressure in postmenopausal women.

Keywords

blood pressure eNOS gene polymorphism physical exercise women

Get full access to this article

View all access options for this article.

References

1. Moncada

Higgs

EA.

Endogenous nitric oxide: physiology, pathology and clinical relevance. Eur J Clin Invest 1991; 21:361–374.

2. Boo

Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases. Am J Physiol Cell Physiol 2003; 285:499–508.

3. Zanesco

Antunes

Effects of exercise training on the cardiovascular system: pharmacological approaches. Pharmacol Ther 2007; 114:307–317.

4. Claudino

Franco-Penteado

Priviero

Camargo

Teixeira

Muscará

. Up-regulation of gp91 phox subunit of NAD(P)H oxidase contributes to erectile dysfunction caused by long-term nitric oxide inhibition in rats: reversion by regular physical training. Urology 2010; 75:961–967.

5. Zaros

Pires

Bacci

Jr Moraes

Zanesco

Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women. BMC Womens Health 2009; 19:9–17.

6. Kodja

Cheng

Burchfield

Harrison

DG.

Dysfunctional regulation of endothelial nitric oxide synthase (eNOS) expression in response to exercise in mice lacking one eNOS gene. Circulation 2001; 103:2839–2844.

7. Mombouli

Nakashima

Hamra

Vanhoutte

PM.

Endothelium-dependent relaxation and hyperpolarization evoked by bradykinin in canine coronary arteries: enhancement by exercise-training. Br J Pharmacol 1996; 117:413–418.

8. Oltman

Parker

Laughlin

MH.

Endothelium-dependent vasodilation of proximal coronary arteries from exercise-trained pigs. J Appl Physiol 1995; 79:33–40.

9. Claudino

Priviero

Camargo

Teixeira

De Nucci

Antunes

. Protective effect of prior physical conditioning on relaxing response of corpus cavernosum from rats made hypertensive by nitric oxide inhibition. Int J Impot Res 2007; 19:189–195.

10.

10. Delbin

Moraes

Camargo

Mussi

Antunes

de Nucci

Zanesco

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion. Comp Biochem Physiol A Mol Integr Physiol 2007; 147:793–798.

11.

11. Hambrecht

Adams

Erbs

Linke

Kränkel

Shu

. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 2003; 107:3152–3158.

12.

12. Augeri

Tsongalis

Van Heest

Maresh

Thompson

Pescatello

LS.

The endothelial nitric oxide synthase 786 T C polymorphism and the exercise-induced blood pressure and nitric oxide responses among men with elevated blood pressure. Atherosclerosis 2009; 204:E28–E34.

13.

13. Ristow

Zarse

Oberbach

Klöting

Birringer

Kiehntopf

. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A 2009; 106:8665–8670.

14.

14. Simkin-Silverman

Wing

Hansen

Klem

Pasagian-Macaulay

Meilahn

. Prevention of cardiovascular risk factor elevations in healthy premenopausal women. Prev Med 1995; 24:509–517.

15.

15. Simkin-Silverman

Wing

Boraz

Kuller

LH.

Lifestyle intervention can prevent weight gain during menopause: results from a 5-year randomized clinical trial. Ann Behav Med 2003; 26:212–220.

16.

16. Blumenthal

Siegel

Appelbaum

Failure of exercise to reduce blood pressure in patients with mild hypertension: results of a randomized controlled trial. JAMA 1991; 266:2098–2104.

17.

17. Nami

Mondillo

Agricola

Lenti

Ferro

Nami

. Aerobic exercise training fails to reduce blood pressure in nondipper-type hypertension. Am J Hypertens 2000; 13:593–600.

18.

18. Stewart

Bacher

Turner

KL.

Effect of exercise on blood pressure in older persons: a randomized controlled trial. Arch Intern Med 2005; 165:756–762.

19.

19. Miyamoto

Saito

Nakayama

Shimasaki

Yoshimura

. Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a −786T C mutation associated with coronary spastic angina. Hum Mol Genet 2000; 9:2629–2637.

20.

20. Erbs

Baither

Linke

Adams

Shu

Lenk

. Promoter but not exon 7 polymorphism of endothelial nitric oxide synthase affects training-induced correction of endothelial dysfunction. Arterioscler Thromb Vasc Biol 2003; 23:1814–1819.

21.

21. Dosenko

Zagoriy

Lutay

Parkhomenko

Moibenko

AA.

Allelic polymorphism in the promoter (T C), but not in exon 7 (G T) or the variable number tandem repeat in intron 4, of the endothelial nitric oxide synthase gene is positively associated with acute coronary syndrome in the Ukrainian population. Exp Clin Cardiol 2006; 11:11–13.

22.

22. Kline

Porcari

Hintermeister

Freedson

Ward

McCarron

. Estimation of VO_2max from a one-mile track walk, gender, age, and body weight. Med Sci Sports Exerc 1987; 19:253–259.

23.

23. De Moraes

Davel

Rossoni

Antunes

Zanesco

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats. BMC Physiol 2008; 29:8–12.

24.

24. Hansen

Zhang

Gomez

Adams

Schoeller

DA.

Exercise increases the proportions of fat utilization during short term consumption of a high fat diet. Am J Clin Nut 2007; 85:109–116.

25.

25. Staron

Malicky

Leonardi

Falkel

Hagerman

Dudley

GA.

Muscle hypertrophy and fast fiber type conversions in heavy resistance-trained women. Eur J Appl Physiol Occup Physiol 1990; 60:71–79.

26.

26. Sisson

Katzmarzyk

Earnest

Bouchard

Blair

Church

TS.

Volume of exercise and fitness non-response in sedentary, post-menopausal women. Med Sci Sports Exerc 2009; 41:539–545.

27.

27. Metzger

Souza-Costa

Marroni

Nagassaki

Desta

Flockhart

. Endothelial nitric oxide synthase gene haplotypes associated with circulating concentrations of nitric oxide products in healthy men. Pharmacogenet Genomics 2005; 15:565–570.

28.

28. Dengel

Brown

Ferrell

Reynolds

Supiano

MA.

A preliminary study on T-786C endothelial nitric oxide synthase gene and renal hemodynamic and blood pressure responses to dietary sodium. Physiol Res 2007; 56:393–401.

29.

29. Sandrim

de Syllos

Lisboa

Tres

Tanus-Santos

JE.

Influence of eNOS haplotypes on the plasma nitric oxide products concentrations in hypertensive and type 2 diabetes mellitus patients. Nitric Oxide 2007; 16:348–355.

30.

30. Laurent

Daline

Malika

Fawzi

Philippe

Benoit

. Training-induced increase in nitric oxide metabolites in chronic heart failure and coronary artery disease: an extra benefit of water-based exercises? Eur J Cardiovasc Prev Rehab 2009; 16:215–221.

31.

31. Nakayama

Yasue

Yoshimura

Shimasaki

Kugiyama

Ogawa

. T-786 C Mutation in the 5-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 1999; 99:2864–2870.

32.

32. Cattaruzza

Guzik

Slodowski

Pelvan

Becker

Halle

. Shear stress insensitivity of endothelial nitric oxide synthase expression as a genetic risk factor for coronary heart disease. Circ Res 2004; 95:841–847.

33.

33. Erbs

Mobius-Winkler

Linke

Adams

Doll

Gielen

. Both T-786C and G894T polymorphism of endothelial nitric oxide synthase affect in-vitro endothelium-dependent relaxation of internal mammary artery rings from patients with coronary artery disease. Eur J Cardiovasc Prev Rehab 2006; 13:826–831.