Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats
Tóm tắt
Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Male Wistar rats were divided into sedentary (SD); trained (TR); sedentary diet (SDD) and trained diet (TRD) groups. Run training (RT) was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max). Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx-) were measured. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1) was assessed by Western blotting. High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl) and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl). Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml) as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml). On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl). Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM). Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%), but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups) or mesenteric rings (10%, for TR and 17%, to TRD groups) that was accompanied by up-regulation of SOD-1 expression and reduction in triglycerides levels. The improvement in endothelial function by physical preconditioning in mesenteric and aortic arteries from high caloric fed-rats was directly related to an increase in NO bioavailability to the smooth muscle mostly due to SOD-1 up regulation.
Tài liệu tham khảo
Hall JE: Pathophysiology of obesity hypertension. Curr Hypertens Rep. 2000, 2 (2): 139-147. 10.1007/s11906-000-0073-4.
Barter PJ, Rye KA: High density lipoproteins and coronary heart disease. Atherosclerosis. 1996, 121 (1): 1-12. 10.1016/0021-9150(95)05675-0.
Diaz MN, Frei B, Vita JA, Keaney JF: Antioxidants and atherosclerotic heart disease. N Engl J Med. 1997, 337 (6): 408-416. 10.1056/NEJM199708073370607.
Rush JW, Denniss SG, Graham DA: Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity. Can J Appl Physiol. 2005, 30 (4): 442-474.
Luz PL, Favarato D, Laurindo FRM: Oxidative theory of atherosclerosis: why did large trials not show benefits?. Int J Atheroscler. 2006, 1 (2): 124-136.
Naderali EK, Brown MJ, Pickavance LC, Wilding JPH, Doyle PJ, Williams G: Dietary obesity in the rat induces endothelial dysfunction without cause insulin resistance: a possible role for triacylglycerols. Clin Sci. 2001, 101 (5): 499-506. 10.1042/CS20010088.
Naderali EK, Fatani S, Williams G: Chronic withdrawal of a high-palatable obesity-inducing diet completely reverses metabolic and vascular abnormalities associated with dietary-obesity in the rat. Atherosclerosis. 2004, 172 (1): 63-69. 10.1016/j.atherosclerosis.2003.09.021.
Woodman CR, Thompson MA, Turk JR, Laughlin MH: Endurance exercise training improves endothelium-dependent relaxation in brachial arteries from hypercholesterolemic male pigs. J Appl Physiol. 2005, 99 (4): 1412-1421. 10.1152/japplphysiol.00293.2005.
Turk JR, Henderson KK, Vanvickle GD, Watkins J, Laughlin MH: Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease. Int J Exp Pathol. 2005, 86 (5): 335-345. 10.1111/j.0959-9673.2005.00446.x.
Halverstadt A, Phares DA, Wilund KR, Goldberg AP, Hagberg JM: Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women. Metabolism. 2007, 56 (4): 444-450. 10.1016/j.metabol.2006.10.019.
Delp MD, McAllister RM, Laughlin MH: Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta. J Appl Physiol. 1993, 75 (3): 1354-1363.
Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH: Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res. 1994, 74 (2): 349-353.
Shen W, Lundborg M, Wang J, Stewart JM, Xu X, Ochoa M, Hintze TH: Role of EDRF in the regulation of regional blood flow and vascular resistance at rest and during exercise in conscious dogs. J Appl Physiol. 1994, 77 (1): 165-172.
Woodman CR, Muller JM, Laughlin MH, Price EM: Induction of nitric oxide synthase mRNA in coronary resistance arteries isolated from exercise-trained pigs. Am J Physiol. 1997, 273 (6): H2575-2579.
Kingwell BA: Nitric oxide-mediated metabolic regulation during exercise: effects of training in health and cardiovascular disease. FASEB J. 2000, 14 (12): 1685-1696. 10.1096/fj.99-0896rev.
Maeda S, Miyauch T, Kakiyama T, Sugawara J, Iemitsu M, Irukayama-Tomobe Y, Murakami H, Kumagai Y, Kuno S, Matsuda M: Effects of exercise training of 8 weeks and detraininig on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans. Life Sci. 2001, 69 (9): 1005-1016. 10.1016/S0024-3205(01)01192-4.
Maiorana A, O'Driscoll G, Taylor R, Green D: Exercise and the nitric oxide vasodilator system. Sports Med. 2003, 33 (14): 1013-1035. 10.2165/00007256-200333140-00001.
Dobrian AD, Davies MJ, Prewitt RL, Lauterio TJ: Development of hypertension in a rat model of diet-induced obesity. Hypertension. 2000, 35 (4): 1009-1015.
Herbert V, Lau KS, Gottlieb CW, Bleicher SJ: Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965, 25 (10): 1375-1384.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28 (7): 412-419. 10.1007/BF00280883.
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976, 7 (72): 248-254. 10.1016/0003-2697(76)90527-3.
Tschöp M, Heiman ML: Rodent obesity models: an overview. Exp Clin Endocrinol & Diabetes. 2001, 109 (6): 307-319. 10.1055/s-2001-17297.
Naderali EK, Williams G: Prolonged endothelial-dependent and -independent arterial dysfunction induced in the rat by short-term feeding with a high-fat, high-sucrose diet. Atherosclerosis. 2003, 166 (2): 253-259. 10.1016/S0021-9150(02)00367-2.
Kougias P, Chai H, Lin PH, Yao Q, Lumsden AB, Chen C: Effects of adipocyte-derived cytokines on endothelial functions: implication ofvascular disease. J Surg Res. 2005, 126 (1): 121-129. 10.1016/j.jss.2004.12.023.
Galili O, Versari D, Sattler KJ, Olson ML, Mannheim D, McConnell JP, Chade AR, Lerman LO, Lerman A: Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. Am J Physiol Heart Circ Physiol. 2007, 292 (2): H904-911. 10.1152/ajpheart.00628.2006.
Fortuño A, San José G, Moreno MU, Díez J, Zalba G: Oxidative stress and vascular remodeling. Exp Physiol. 2005, 90 (4): 457-462. 10.1113/expphysiol.2005.030098.
Oscai LB, Essig DA, Palmer WK: Lipase regulation of muscle triglyceride hydrolysis. J Appl Physiol. 1990, 69 (5): 1571-1577.
Hennig B, Toborek M, McClain CJ: High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis. J Am Coll Nutr. 2001, 20 (2 suppl): 97-105.
Barnard RJ, Roberts CK, Varon SM, Berger JJ: Diet-induced insulin resistance precedes other aspects of the metabolic syndrome. J Appl Physiol. 1998, 84 (4): 1311-1315.
Straczkowski M, Kowalska I, Dzienis-Straczkowska S, Kinalski M, Górski J, Kinalska I: The effect of exercise training on glucose tolerance and skeletal muscle triacylglycerol content in rats fed with a high-fat diet. Diabetes Metab. 2001, 27 (1): 19-23.
Krebs M, Roden M: Molecular mechanisms of lipid-induced insulin resistance in muscle, liver and vasculature. Diabetes Obes Metab. 2005, 7 (6): 621-632. 10.1111/j.1463-1326.2004.00439.x.
López IP, Marti A, Milagro FI, Zulet Md Mde L, Moreno-Aliaga MJ, Martinez JA, De Miguel C: DNA microarray analysis of genes differentially expressed in diet-induced (cafeteria) obese rats. Obes Res. 2003, 11 (2): 188-194. 10.1038/oby.2003.30.
Estadella D, Oyama LM, Dâmaso AR, Ribeiro EB, Oller Do Nascimento CM: Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats. Nutrition. 2004, 20 (2): 218-224. 10.1016/j.nut.2003.10.008.
Higashi Y, Yoshizumi M: Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacol Ther. 2004, 102 (1): 87-96. 10.1016/j.pharmthera.2004.02.003.
Zanesco A, Antunes E: Effects of exercise training on the cardiovascular system: Pharmacological approaches. Pharmacol Ther. 2007, 114 (3): 307-317. 10.1016/j.pharmthera.2007.03.010.
Droge W: Free radicals in the physiological control of cell function. Physiol Rev. 2002, 82 (1): 47-95.
Dimmeler S, Fleming I, Fisslthalter B, Hermann C, Busse R, Zeiher AM: Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999, 399 (6736): 601-605. 10.1038/21224.
Davis KL, Martin E, Turko IV, Murad F: Novel effects of nitric oxide. Annu Rev Pharmacol Toxicol. 2001, 41: 203-236. 10.1146/annurev.pharmtox.41.1.203.
Davis ME, Cai H, McCann L, Fukai T, Harrison DG: Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. Am J Physiol Heart Circ Physiol. 2003, 284 (4): H1449-1453.
Inoue N, Ramasamy S, Fukai T, Nerem RM, Harrison DG: Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells. Circ Res. 1996, 79 (1): 32-37.
Fukai T, Folz RJ, Landmesser U, Harrison DG: Extracellular superoxide dismutase and cardiovascular disease. Cardiovasc Res. 2002, 55 (2): 239-249. 10.1016/S0008-6363(02)00328-0.
Rush JW, Turk JR, Laughlin MH: Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. Am J Physiol Heart Circ Physiol. 2003, 284 (4): H1378-1387.
Thompson MA, Henderson KK, Woodman CR, Turk JR, Rush JW, Price E, Laughlin MH: Exercise preserves endothelium-dependent relaxation in coronary arteries of hypercholesterolemic male pigs. J Appl Physiol. 2004, 96 (3): 1114-1126. 10.1152/japplphysiol.00768.2003.
Oltman CL, Parker JL, Adams HR, Laughlin MH: Effects of exercise training on vasomotor reactivity of porcine coronary arteries. Am J Physiol. 1992, 263 (2 Pt 2): H372-382.
McAllister RM, Kimani JK, Webster JL, Parker JL, Laughlin MH: Effects of exercise training on responses of peripheral and visceral arteries in swine. J Appl Physiol. 1996, 80 (1): 216-225. 10.1063/1.362807.
Jasperse JL, Laughlin MH: Vasomotor responses of soleus feed arteries from sedentary and exercise-trained rats. J Appl Physiol. 1999, 86 (2): 441-449.
Henderson KK, Turk JR, Rush JW, Laughlin MH: Endothelial function in coronary arterioles from pigs with early-stage coronary disease induced by high-fat, high-cholesterol diet: effect of exercise. J Appl Physiol. 2004, 97 (3): 1159-1168. 10.1152/japplphysiol.00261.2004.
De Moraes C, Camargo EA, Antunes E, De Nucci G, Zanesco A: Reactivity of mesenteric and aortic rings from trained rats feed with high caloric diet. Comp Biochem Physiol A. 2007, 147 (3): 788-792. 10.1016/j.cbpa.2006.10.018.