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Arginine and aerobic training prevent endothelial and metabolic alterations in rats at high risk for the development of the metabolic syndrome

  • Renata F. Medeiros (a1), Thaiane G. Gaique (a1), Thais Bento-Bernardes (a1), Raquel Kindlovits (a1), Tamiris M. B. Gomes (a1), Nadia Alice V. Motta (a1), Fernanda Carla Brito (a1), Caroline Fernandes-Santos (a2), Karen J. Oliveira (a1) and Antonio Claudio L. Nóbrega (a1)...
Abstract
Abstract

Endothelial function is a key mechanism in the development of CVD. Arginine and exercise are important non-pharmacological strategies for mitigating the impact of metabolic changes in the metabolic syndrome, but the effect of their combined administration is unknown. Thus, the aim of this study was to investigate the isolated and combined effects of aerobic training and arginine supplementation on metabolic variables and vascular reactivity in rats at high risk for developing the metabolic syndrome. Wistar rats were divided into two groups: control and fructose (F – water with 10 % fructose). After 2 weeks, the F group was divided into four groups: F, fructose+arginine (FA, 880 mg/kg per d of l-arginine), fructose+training (FT) and fructose+arginine+training (FTA); treatments lasted for 8 weeks, and no difference was observed in body mass gain. Arginine did not improve the body protein content, and both the FA and FT groups show a reversal of the increase in adipose tissue. Insulin increase was prevented by training and arginine, without additive effect, and the increase in serum TAG was prevented only by training. The F group showed impaired endothelium-dependent vasodilation and hyperreactivity to phenylephrine, but arginine and training were capable of preventing these effects, even separately. Higher nitric oxide level was observed in the FA and FT groups, and no potentiating effect was detected. Thus, only training was able to prevent the increase in TAG and improve the protein mass, and training and arginine exert similar effects on fat content, insulin and endothelial function, but these effects are not additive.

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* Corresponding author: R. F. Medeiros, email frauches.renata@gmail.com
References
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1. AlwanA, ArmstrongT, CowanM, et al. (2011) WHO maps noncommunicable disease trends in all countries: country profiles on noncommunicable disease trends in 193 countries. Cent Eur J Public Health 19, 130, 138.
2. BascianoH, FedericoL & AdeliK (2005) Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond) 2, 5.
3. SmithSCJr, GreenlandP & GrundySM (2000) AHA Conference Proceedings. Prevention conference V: Beyond secondary prevention: Identifying the high-risk patient for primary prevention: executive summary. American Heart Association. Circulation 101, 111116.
4. EckelRH, YorkDA, RossnerS, et al. (2004) Prevention Conference VII: Obesity, a worldwide epidemic related to heart disease and stroke: executive summary. Circulation 110, 29682975.
5. GrundySM, GarberA, GoldbergR, et al. (2002) Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group IV: lifestyle and medical management of risk factors. Circulation 105, e153e158.
6. BantleJP, SwansonJE, ThomasW, et al. (1992) Metabolic effects of dietary fructose in diabetic subjects. Diabetes Care 15, 14681476.
7. MedeirosRF, GaiqueTG, Bento-BernardesT, et al. (2016) Aerobic training prevents oxidative profile and improves nitric oxide and vascular reactivity in rats with cardiometabolic alteration. J Appl Physiol 121, 289298.
8. NadeVS, KawaleLA, TodmalUB, et al. (2012) Effect of bromocriptine on cardiovascular complications associated with metabolic syndrome in fructose fed rats. Indian J Pharmacol 44, 688693.
9. ChouCL, PangCY, LeeTJ, et al. (2013) Direct renin inhibitor prevents and ameliorates insulin resistance, aortic endothelial dysfunction and vascular remodeling in fructose-fed hypertensive rats. Hypertens Res 36, 123128.
10. MahmoudMF, El-NagarM & El-BassossyHM (2012) Anti-inflammatory effect of atorvastatin on vascular reactivity and insulin resistance in fructose fed rats. Arch Pharm Res 35, 155162.
11. ParkMH, FalconerC, VinerRM, et al. (2012) The impact of childhood obesity on morbidity and mortality in adulthood: a systematic review. Obes Rev 13, 9851000.
12. World Health Organization (2011) Scaling Up Action Against Noncommunicable Diseases: How Much Will it Cost?. Geneva: WHO.
13. VitaJA & KeaneyJFJr (2002) Endothelial function: a barometer for cardiovascular risk? Circulation 106, 640642.
14. RossR (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801809.
15. MuiesanML, SalvettiM, PainiA, et al. (2008) Prognostic role of flow-mediated dilatation of the brachial artery in hypertensive patients. J Hypertens 26, 16121618.
16. NaqviTZ & HyuhnHK (2009) Cerebrovascular mental stress reactivity is impaired in hypertension. Cardiovasc Ultrasound 7, 32.
17. IiyamaK, NaganoM, YoY, et al. (1996) Impaired endothelial function with essential hypertension assessed by ultrasonography. Am Heart J 132, 779782.
18. MoncadaS & HiggsA (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329, 20022012.
19. CookeJP, AndonNA, GirerdXJ, et al. (1991) Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta. Circulation 83, 10571062.
20. CookeJP, SingerAH, TsaoP, et al. (1992) Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. J Clin Invest 90, 11681172.
21. Bode-BogerSM, MukeJ, SurdackiA, et al. (2003) Oral l-arginine improves endothelial function in healthy individuals older than 70 years. Vasc Med 8, 7781.
22. CreagerMA, GallagherSJ, GirerdXJ, et al. (1992) L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. Journal Clin Invest 90, 12481253.
23. GornikHL & CreagerMA (2004) Arginine and endothelial and vascular health. J Nutr 134, 2880S2887S; discussion 2895S.
24. Bode-BogerSM, BogerRH, GallandA, et al. (1998) L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol 46, 489497.
25. ThompsonPD, BuchnerD, PinaIL, et al. (2003) Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 107, 31093116.
26. FletcherGF, BaladyG, BlairSN, et al. (1996) Statement on exercise: benefits and recommendations for physical activity programs for all Americans. A statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation 94, 857862.
27. MannS, BeedieC & JimenezA (2014) Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports Med 44, 211221.
28. WheltonSP, ChinA, XinX, et al. (2002) Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med 136, 493503.
29. ThomasDE, ElliottEJ & NaughtonGA (2006) Exercise for type 2 diabetes mellitus. The Cochrane Database of Systematic Reviews 2006, 19, CD002968.
30. SzostakJ & LaurantP (2011) The forgotten face of regular physical exercise: a ‘natural’ anti-atherogenic activity. Clin Sci (Lond) 121, 91106.
31. MoraS, CookN, BuringJE, et al. (2007) Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation 116, 21102118.
32. JoynerMJ & GreenDJ (2009) Exercise protects the cardiovascular system: effects beyond traditional risk factors. J Physiol 587, 55515558.
33. BeerePA, GlagovS & ZarinsCK (1992) Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. Localization, compensatory enlargement, and the sparing effect of lowered heart rate. Arterioscler Thromb 12, 12451253.
34. ForjazCL, TinucciT, OrtegaKC, et al. (2000) Factors affecting post-exercise hypotension in normotensive and hypertensive humans. Blood Press Monit 5, 255262.
35. KulicsJM, CollinsHL & DiCarloSE (1999) Postexercise hypotension is mediated by reductions in sympathetic nerve activity. Am J Physiol 276, H27H32.
36. MuriasJM, DeyA, CamposOA, et al. (2013) High-intensity endurance training results in faster vessel-specific rate of vasorelaxation in type 1 diabetic rats. PLOS ONE 8, e59678.
37. Reagan-ShawS, NihalM & AhmadN (2008) Dose translation from animal to human studies revisited. FASEB J 22, 659661.
38. SianiA, PaganoE, IaconeR, et al. (2000) Blood pressure and metabolic changes during dietary L-arginine supplementation in humans. Am J Hypertens 13, 547551.
39. SunL, LiuQ & FanJ (2017) Comparison of free total amino acid Compositions and their functional classifications in 13 wild edible mushrooms. Molecules 22, 350.
40. VarnamA & SutherlandJM (1995) Meat and Meat Products: Technology, Chemistry and Microbiology, vol. 3. Berlin: Springer.
41. PaulaGS, SouzaLL, CabanelasA, et al. (2010) Female mice target deleted for the neuromedin B receptor have partial resistance to diet-induced obesity. J Physiol 588, 16351645.
42. GomesVA, Casella-FilhoA, ChagasAC, et al. (2008) Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome. Nitric Oxide 19, 345350.
43. SouzaLL, CordeiroA, OliveiraLS, et al. (2011) Thyroid hormone contributes to the hypolipidemic effect of polyunsaturated fatty acids from fish oil: in vivo evidence for cross talking mechanisms. J Endocrinol 211, 6572.
44. da MottaNA, KummerleAE, MarosticaE, et al. (2013) Anti-atherogenic effects of a new thienylacylhydrazone derivative, LASSBio-788, in rats fed a hypercholesterolemic diet. J Pharmacol Sci 123, 4757.
45. MorrisM, AraujoIC, PohlmanRL, et al. (2012) Timing of fructose intake: an important regulator of adiposity. Clin Exp Pharmacol Physiol 39, 5762.
46. YooS, AhnH & ParkYK (2016) High dietary fructose intake on cardiovascular disease related parameters in growing rats. Nutrients 9, 11.
47. JinR, WelshJA, LeNA, et al. (2014) Dietary fructose reduction improves markers of cardiovascular disease risk in Hispanic-American adolescents with NAFLD. Nutrients 6, 31873201.
48. WilkesJJ, HevenerA & OlefskyJ (2003) Chronic endothelin-1 treatment leads to insulin resistance in vivo . Diabetes 52, 19041909.
49. IbrahimMA, AminEF, IbrahimSA, et al. (2014) Montelukast and irbesartan ameliorate metabolic and hepatic disorders in fructose-induced metabolic syndrome in rats. Eur J Pharmacol 724, 204210.
50. de MouraRF, RibeiroC, de OliveiraJA, et al. (2009) Metabolic syndrome signs in Wistar rats submitted to different high-fructose ingestion protocols. Br J Nutr 101, 11781184.
51. KimHY, OkuboT, JunejaLR, et al. (2010) The protective role of amla (Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome in a rat model. Br J Nutr 103, 502512.
52. CunhaTF, BecharaLR, BacurauAV, et al. (2017) Exercise training decreases NADPH oxidase activity and restores skeletal muscle mass in heart failure rats. J Appl Physiol 122, 817–827.
53. PowersSK, LennonSL, QuindryJ, et al. (2002) Exercise and cardioprotection. Curr Opin Cardiol 17, 495502.
54. EmterCA, McCuneSA, SparagnaGC, et al. (2005) Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 289, H2030H2038.
55. RovedaF, MiddlekauffHR, RondonMU, et al. (2003) The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial. J Am Coll Cardiol 42, 854860.
56. AlvaresTS, Conte-JuniorCA, SilvaJT, et al. (2014) L-arginine does not improve biochemical and hormonal response in trained runners after 4 weeks of supplementation. Nutr Res 34, 3139.
57. DoutreleauS, MettauerB, PiquardF, et al. (2006) Chronic L-arginine supplementation enhances endurance exercise tolerance in heart failure patients. Int J Sports Med 27, 567572.
58. De AngelisK, SenadorDD, MostardaC, et al. (2012) Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice. Am J Physiol Regul Integr Comp Physiol 302, R950R957.
59. SugaA, HiranoT, KageyamaH, et al. (2000) Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats. Am J Physiol Endocrinol Metab 278, E677E683.
60. MadaniZ, LouchamiK, SenerA, et al. (2012) Dietary sardine protein lowers insulin resistance, leptin and TNF-alpha and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome. Int J Mol Med 29, 311318.
61. BogdanskiP, SuliburskaJ, GrabanskaK, et al. (2012) Effect of 3-month l-arginine supplementation on insulin resistance and tumor necrosis factor activity in patients with visceral obesity. Eur Rev Med Pharmacol Sci 16, 816823.
62. LucottiP, MontiL, SetolaE, et al. (2009) Oral L-arginine supplementation improves endothelial function and ameliorates insulin sensitivity and inflammation in cardiopathic nondiabetic patients after an aortocoronary bypass. Metabolism 58, 12701276.
63. MiczkeA, SuliburskaJ, Pupek-MusialikD, et al. (2015) Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet. Int J Clin Exp Med 8, 1035810366.
64. MatravadiaS, ZabielskiP, ChabowskiA, et al. (2016) LA and ALA prevent glucose intolerance in obese male rats without reducing reactive lipid content, but cause tissue-specific changes in fatty acid composition. Am J Physiol Regul Integr Comp Physiol 310, R619R630.
65. GrundySM, BlackburnG, HigginsM, et al. (1999) Physical activity in the prevention and treatment of obesity and its comorbidities: evidence report of independent panel to assess the role of physical activity in the treatment of obesity and its comorbidities. Med Sci Sports Exer 31, 14931500.
66. LakkaTA & LaaksonenDE (2007) Physical activity in prevention and treatment of the metabolic syndrome. Applied Physiol Nutr Metab 32, 7688.
67. FuWJ, HaynesTE, KohliR, et al. (2005) Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr 135, 714721.
68. WuZ, PuigserverP, AnderssonU, et al. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115124.
69. LehmanJJ, BargerPM, KovacsA, et al. (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106, 847856.
70. ChromiakJA & Antonio J (2002) Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 18, 5.
71. IshiyamaN, RavierMA & HenquinJC (2006) Dual mechanism of the potentiation by glucose of insulin secretion induced by arginine and tolbutamide in mouse islets. Am J Physiol Endocrinol Metab 290, E540E549.
72. UmpierreD, RibeiroPA, KramerCK, et al. (2011) Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 305, 17901799.
73. WayKL, HackettDA, BakerMK, et al. (2016) The effect of regular exercise on insulin sensitivity in type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Metab J 40, 253271.
74. KawanoT, NomuraM, NisikadoA, et al. (2003) Supplementation of L-arginine improves hypertension and lipid metabolism but not insulin resistance in diabetic rats. Life Sci 73, 30173026.
75. PaolissoG, TagliamonteMR, MarfellaR, et al. (1997) L-arginine but not D-arginine stimulates insulin-mediated glucose uptake. Metabolism 46, 10681073.
76. FraynKN, ArnerP & Yki-JarvinenH (2006) Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem 42, 89103.
77. AndrewPJ & MayerB (1999) Enzymatic function of nitric oxide synthases. Cardiovasc Res 43, 521531.
78. WilsonAM, HaradaR, NairN, et al. (2007) L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation 116, 188195.
79. BaiY, SunL, YangT, et al. (2009) Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr 89, 7784.
80. SunD, HuangA, KollerA, et al. (1994) Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats. J App Physiol 76, 22412247.
81. CarvalhoDS, DinizMM, HaidarAA, et al. (2016) L-Arginine supplementation improves insulin sensitivity and beta cell function in the offspring of diabetic rats through AKT and PDX-1 activation. Eur J Pharmacol 791, 780787.
82. HambrechtR, HilbrichL, ErbsS, et al. (2000) Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J Am Coll Cardiol 35, 706713.
83. TsikasD, BogerRH, SandmannJ, et al. (2000) Endogenous nitric oxide synthase inhibitors are responsible for the L-arginine paradox. FEBS Lett 478, 13.
84. GirerdXJ, HirschAT, CookeJP, et al. (1990) L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits. Circ Res 67, 13011308.
85. GarciaVP, RochaHN, SilvaGM, et al. (2016) Exogenous l-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension. Life Sci 157, 125130.
86. CaiH & HarrisonDG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87, 840844.
87. AndoK & FujitaT (2009) Metabolic syndrome and oxidative stress. Free Radic Biol Med 47, 213218.
88. FurukawaS, FujitaT, ShimabukuroM, et al. (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114, 17521761.
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British Journal of Nutrition
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