A Study of L-Arginine to Asymmetric Dimethylarginine Ratio in Middle Aged Hypertensive Men and Effect of Aerobic Training on this Variable

Document Type : Original Article

Authors

1 Department of Physical Edu, Shahid Rajaee Teacher Treaining University, Tehran. Iran.

2 Department of Physical Education & Sport Sciences, SHahid Rajaee Teacher Treaining University of Tehran, Iran.

3 Department of Physical Education & Sport Sciences of kharazmi University of Tehran, Iran.

4 Department of General Surgery, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

Background and Objective: Endothelial function has an effect on blood pressure and meanwhile, the ratio of L-Arginine/Asymmetric Dimethylarginine (L-Arg/ ADMA) is important. In addition, the effect of exercise training on blood pressure has been established. The present study intends to examine LArg / ADMA ratio in patients with hypertensive middle-aged men and the effect of aerobic trainingon it.
Subjects and Methods: In this quasi-experimental study, 12 normo-tensive and 24 hypertensive middle-aged men (age: 49.66 ± 2.8 y, height: 174.16 ± 4.66 cm, weight: 81.08 ± 12.65 Kg) were selected. The hypertensive subjects were further sub-divided into two groups. 12 for control (age: 52.08 ± 2.53 y, height: 173.75 ± 5.81 cm, weight: 80.08 ± 8.26 Kg) and 12 for aerobic training (age: 50.54 ± 3.01 y, height: 177.01 ± 5.98 cm, weight: 86.09 ± 13.15 Kg). The training included 12 wks treadmill aerobic running with 60 % heart rate reserve, three times-a-week for 12 min each session. each week up to the 6th week 3 min and then every two weeks 3 min were added to the training time. So that training in the last two weeks was 36 min. Blood pressure and samples for the measurement of L-Arg/ADMA ratio were taken before and after the training period. Blood variables were measured by ELISA method. Normality of distribution of data was assessed with the Shapiro-Wilk test and between subjects differences was assessed with independent t-test and analysis of variance with repeated measures.
Results: Results showed that the L-Arg/ADMA ratio is more in patients than in healthy subjects (t=5.099, P=0.0001) and sub maximal aerobic training significantly reduced systolic blood pressure (F=8.698, P=0.008) and increased L-Arg /ADMA (F=10.741, P=0.004).
Conclusion: It seems that endothelial function in patients with hypertension is impaired and these patients can do aerobic training to relieve pressure and improve endothelial function.
 

Keywords

References

 
1-Cooke JP, Dzau VJ. Nitric oxide synthase: role in the genesis of vascular disease. Annu Rev Med. 1997;48:489-509.
2-Moncada S, Higgs EA. The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol. 2006; 147: S193-201.
3-Davids M, Teerlink T. Asymmetric dimethylarginine (ADMA) and cardiovascular disease. Ned Tijdschr Klin Chem Labgeneesk 2012; 37: 10-14.
4-Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, et al. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999;99:1141–6.
5-Wang D, Strandgaard S, Iversen J, Wilcox CS. Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension. Am J Physiol Regul Integr Comp Physiol 2009;296:R195–200.
6-Surdacki A, Nowicki M, Sandmann J, Tsikas D, Boeger RH, Bode-Boger SM, et al. Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol 1999;33:652–8.
7-Boger RH, Sullivan LM, Schwedhelm E, Wang TJ, Maas R, Benjamin EJ, et al. Plasma asymmetric dimethylarginine and incidence of cardiovascular disease and death in the community. Circulation 2009;119:1592-600.
8-Delles C, Schneider MP, John S, Gekle M, Schmieder RE. Angiotensin converting enzyme inhibition and angiotensin II AT1 receptor blockade reduce the levels of asymmetrical NG,NG-dimethylarginine in human essential hypertension. Am J Hypertens 2002;15:590–3.
9-Boger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the “l-arginine paradox” and acts as a novel cardiovascular risk factor. J Nutr 2004;134:284 2-7.
10-Böger R H, Ron E S.   L-Arginine Improves Vascular Function by Overcoming the Deleterious Effects of ADMA, a Novel Cardiovascular Risk Factor. Altern Med Rev 2005;10(1):14-23.
11-Bode-B€oger SM, Muke J, Surdacki A, Brabant G, Boger RH, Frolich JC. Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Vasc Med 2003;8:77-81.
12-Bode-B€oger SM, Boger RH, Kienke S, Junker W, Frolich JC. Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. Biochem Biophys Res Commun 1996;219:598-603.
13-Eid HM, Eritsland J, Larsen J, Arnesen H, Seljeflot I. Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin. Atherosclerosis 2003;166:279-84.
14-Seljeflot I,  Nilsson B B, Westheim A S, Bratseth V, Arnesen H. The L-rginineAsymmetric Dimethylarginine Ratio Is StronglyRelated to the Severity of Chronic Heart Failure. No Effects ofExercise Training. J Cardiac Fail 2011;17:135-142.
15-Ruivo J A, Alcântara P. Hypertension and exercise. Rev Port Cardiol. 2012;31(2):151-158.
16-Kokkinos P, Narayan P, Papademetriou V. Exercise as hypertension therapy. Cardiol Clin. 2001;19:507-516.
17-Hagberg J, Park JJ, Brown M. The role of exercise training in the treatment of hypertension --- an update. Sports Med. 2000;30:193-206.
18-Madanmohan, Bhavanani A B,Sanjay Z, Vithiyalakshmi L, Dayanidy G. Effects of eight week yoga therapy program on cardiovascular health in hypertensives. Indian Journal of Traditional Knowledge 2013; Vol. 12 (3), 535-541.
19-Muhihi A, Njelekela M, Mpembeni R, Masesa Z, Kitamori K, Mori M, Kato N, Mtabaji J, Yamori Y. Physical activity and cardiovascular disease risk factors among young and middleaged men in urban Mwanza, Tanzania. P an African Medical Journal 2012; 1937- 8688.
20-Archer E, Blair S N. Physical Activity and the Prevention of Cardiovascular Disease: From Evolution to Epidemiology. Prog Cardiovasc Dis 2011;53:387-396.
21-Yung LM, Laher I, Yao X, et al. Exercise, vascular wall and cardiovascular diseases: an update (part 2). Sports Med. 2009;39:45-63.
22-Zhang J, Ren CX, Qi YF, et al. Exercise training promotes expression of apelin and APJ of cardiovascular tissues in spontaneously hypertensive rats. Life Sci. 2006;79:1153-9.
23-Nemoto KI, Gen-no H, Masuki S, et al. Effects of highintensity interval walking training on physical fitness and blood pressure in middle-aged and older people. Mayo Clin Proc. 2007;82:803-11.
24-KayrakM, BacaksizA, VatankuluMA, AyhanS S, TanerA, UnluA, YaziciM, UlgenM. Association Between Exaggerated Blood Pressure Responseto Exercise and Serum Asymmetric Dimethylarginine Levels. Circ J 2010; 74: 1135 – 1141.
25-Ruffolo RRJ, Feuerstein GZ. Neurohormonal activation, oxygen freeradicals, and apoptosis in the pathogenesis of congestive heart failure.J Cardiovasc Pharmacol 1998;32:S22-30.
26-Esfahani P S, Gharakhanlou R, Karimian J, Khazaei M, Feizi A, Safarzade A. Effect of Resistance Training on Plasma Nitric Oxide and Asymmetric Dimethylarginine Concentrations in Type I Diabetic Rats. Int J Prev Med 2013;4:S78-84.
27-Schlager O, Giurgea A, Schuhfried O,Seidinger D, Hammer A, Gröger M, Moser V F, Gschwandtner M, Koppensteiner R, Steiner S. Exercise training increases endothelial progenitor cells and decreases asymmetric dimethylarginine in peripheral arterial disease: A randomized controlled trial. Atherosclerosis 2011; 217 :240–248.
28-Pickering TG, White WB, on behalf of the American Society of Hypertension Writing Group. When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc Hypertens. 2008; 2(3):119–124.
29-Guimara˜es G  V, Ciolac E G, Carvalho V O, D’Avila V M, Bortolotto L A, Bocchi E A. Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertension Research  2010; 33, 627–632.
30-Tayeh O, Fahmi A, Islam M, Saied M. Asymmetricdimethylarginine as a prognostic markerfor cardiovascular complications in hypertensive patients. The Egyptian Heart Journal 2011; 63, 117–124.
31-Perticone F, Sciacqua A, Maio R, Perticone M, Maas R, Boger R H, Tripepi G, Sesti G, Zoccali C. Asymmetric Dimethylarginine, L-Arginine, and Endothelial Dysfunction in Essential Hypertension. Journal of the American College of Cardiology 2005; Vol. 46, No 3.
32-Wang H, LiuJ. Plasma asymmetric dimethylarginine and l-arginine levelsin Chinese patients with essential hypertension withoutcoronary artery disease. Journal of Cardiovascular Disease Research Vol. 2: No 3: 177-180.
33-Oparil S, Zaman A. Calhoun D A. Pathogenesis of Hypertension. Ann Intern Med. 2003;139:761-776.
34-Huang P L. Disruption of the endothelial nitric oxide synthase gene: effect on vascular response to injury. Am J Cardiol. 1998;82(10A):57S–59S.
35-Cooke J P, Singer A H, Tsao P S, Zera P, Rowan R A, Billingham M E. Anti-atherogenic effects of L-arginine in the hypercholesterolemic rabbit. J Clin Invest. 1992;90:1168 –1172.
36-McNamara D B, Bedi B, Aurora H, Tena L, Ignarro L J, Kadowitz P J, Akers D L. L-Arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Commun. 1993;193:291–296.
37-Tarry W C, Makhoul R G. L-Arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. Arterioscler Thromb. 1994;14:938 –943.
38-Mu¨gge A, Elwell J H, Peterson T E, Hofmeyer T G, Heistad D D, Harrison D G. Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ Res. 1991;69:1293–1300.
39-Gokce N, Keaney J F Jr, Frei B, Holbrook M, Olesiak M, Zachariah B J, Leeuwenburgh C, Heinecke J W, Vita JA. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation. 1999;99:3234 –3240.
40-Ramasamy S, Drummond G R, Ahn J, Storek M, Pohl J, Parthasarathy S, Harrison D G. Modulation of expression of endothelial nitric oxide synthase by nordihydroguaiaretic acid, a phenolic antioxidant in cultured endothelial cells. Mol Pharmacol. 1999;56:116 –123.
41-Hristina K, Langerholc T, Trapecar M. novel metabolic roles of L-Arginine in body energy metabolism and possible clinical applications. The Journal of Nutrition, Health & Aging. 2014; Volume 18, Number 2.  
42-Monti L D, Casiraghi M C, Setola E, Galluccio E, Pagani M A, Quaglia L, Bosi E, Piatti P. L-arginine enriched biscuits improve endothelial function and glucose metabolism: a pilot study in healthy subjects and a cross-over study in subjects with impaired glucose tolerance and metabolic syndrome. Metabolism 2013;62(2):255-64.
43-Paiva H, Laakso J, Kahonen M, Turjanmaa V, Koobi T, Silja, Majahalme S, Lehtimaki T, Inkeri, Ruokonen R, Laaksonen R. Asymmetric dimethylarginine and hemodynamic regulation in middle-aged men. Metabolism Clinical and Experimental 2006; 55: 771– 777.
44-Tanahashi K, Akazawa N, Miyaki A, Choi Y, Ra SG, Matsubara T, Kumagai H, Oikawa S, Maeda S.  Aerobic Exercise Training Decreases Plasma Asymmetric Dimethylarginine Concentrations With Increase in Arterial Compliance in Postmenopausal Women. Am J Hypertens. 2014;27(3):415-21.
45-Tanahashi K, Akazawa N, Miyaki A, Choi Y, Ra SG, Matsubara T, Kumagai H, Oikawa S, Maeda S. Plasma ADMA concentrations associate with aerobic fitness in postmenopausal women. Life Sciences 2014;108:30–33.
46-MittermayeR F, Pleiner J, Krzyzanowska K, Wiesinger G F, Francesconi M, Wolzt M. Regular physical exercise normalizes elevated asymmetrical dimethylarginine concentrations in patients with Type 1 diabetes mellitus. Wien Klin Wochenschr 2005; 117: 23–24: 816–820.
47-MerinoJ, FerréR, Girona J, Aguas D, Cabré A, Plana N, Vinuesa A, Ibarretxe D, Basora J, Buixadera C, Masana L. Physical activity below the minimum internationalrecommendations improves oxidative stress, ADMAlevels, resting heart rate and small artery endothelialfunction. Clin Invest Arterioscl. 2014; ARTERI-291; No 8.
48-Taskiran B, Altun B U, Vardar S A, Demir A M, Karadag C H, Altun A. Effect of Exercise on ADMA Level in Type 2 Diabetes Mellitus. Balkan Med J 2012; 29: 62-7.
49-Popolo A, Adesso S, Pinto A, Autore G, Marzocco S. l‑Arginine and its metabolites in kidney and cardiovascular Disease. Amino Acids 2014; 46:2271–2286.
50-Seljeflot I,  Nilsson B B, Westheim A S, Bratseth V, Arnesen H. The L-rginineAsymmetric Dimethylarginine Ratio Is StronglyRelated to the Severity of Chronic Heart Failure. No Effects ofExercise Training. J Cardiac Fail 2011;17:135e142.
51-Whelton S P, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002; 2:136(7):493-503.
52-Jarrete  A P, Novais I P, Nunes H A, Puga G M, Delbin M A, Zanesco A. Influence of aerobic exercise training on cardiovascular and endocrine-inflammatory biomarkers in hypertensive postmenopausal women. Journal of Clinical & Translational Endocrinology 2014;1:108-114.
53-Gunjal S, Shinde N, Kazi A, khatri S. Effect of Aerobic Interval Training on Blood Pressure and Myocardial function in Hypertensive Patients. International Journal of Pharmaceutical Science Invention 2013; Volume 2 Issue 6: 27-31.
Jundishapur Scientific Medical Journal
Volume 15, Issue 6 - Serial Number 105
January and February 2017
Pages 745-756

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History

  • Receive Date: 22 October 2016
  • Revise Date: 25 December 2016
  • Accept Date: 04 January 2017

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