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Anti-Adhesion Anti-Coagulation Anti- Fibrolysis. Lumen. Shear Stress Insulin Acetylcholine. ↑NO. PI-3 kinase. eNOS. NADPH. Mitochondria. L-arginine O 2. NO. BH 4. ↑NO. Subendothelial Space. Vasodilation. Anti-Adhesion Anti- Coagulation Anti- Fibrolysis. Lumen. ↓NO. eNOS.

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  1. Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Lumen Shear Stress Insulin Acetylcholine ↑NO PI-3 kinase eNOS NADPH Mitochondria L-arginine O2 NO BH4 ↑NO Subendothelial Space Vasodilation

  2. Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Lumen ↓NO eNOS NADPH L-arginine O2 O2- NO O2- BH4 ONOO- ↓NO Subendothelial Space Vasodilation

  3. Ross, R. Atherosclerosis - An inflammatory disease. New England Journal of Medicine 340:115-126, 1999

  4. Shear Stress ↓Ca++ eNOS cGMP Oxygen L-Arginine NADPH Nitric Oxide NO Cofactors VASODILATION i PI-3-Kinase

  5. Post Pre 4.1 mm 4.7 mm ARTERIAL HEALTH Pre Flow-Mediated Dilation = 8%

  6. Faulx, et al, American Heart Journal 145:943-951, 2003 Iiyama, et al. American Heart Journal 132:779-782, 1996 Hashimoto, et al. International Journal of Obesity: RelarMetabDisord 22:477-484, 1998. Caballero, A.E., Obesity Research 11:1278-1289, 2003. Celermajer,et al. J Am CollCardiol 24:471-476, 1994.

  7. Apparently Healthy Hasimoto, et al. Circulation 92:3431-3435, 1995.

  8. Children Woo, et al, International Journal of Obesity 28:852-857, 2004

  9. Aging Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994.

  10. Overweight & Obesity Hashimoto, et al. International Journal of Obesity: Relar Metab Disord 22:477-484, 1998.

  11. Hypertension Iiyama, et al. American Heart Journal 132:779-782, 1996

  12. Diabetes Caballero, A.E., Obesity Research 11:1278-1289, 2003.

  13. Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Blood Flow Insulin Acetylcholine Oxidative Stress ↓NO PI-3 kinase O2- eNOS NADPH L-arginine O2 NO O2- BH4 ONOO- ↓NO Subendothelial Space Vasoconstriction

  14. Endothelial Function of Smokers Celemajer, D, et al Circulation 88:2149-2155, 1999

  15. Endothelial Function of Smokers Celemajer, D, et al Circulation 88:2149-2155, 1999

  16. OXIDATIVE STRESS IN OBESITY Davi, et al. JAMA 288:2008-2014, 2002

  17. OXIDATIVE STRESS FOLLOWING MAXIMAL EXERCISE Vincent, et al. Med Sci Sport Sci, 37:213-219, 2005.

  18. Tsai, et al. Clinical Science 106:315-319, 2004 Anderson, et al, Atherosclerosis 154:475-483, 2001 Ceriello, et al, Circulation 106:1211-1218, 2002

  19. Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Blood Flow Insulin Acetylcholine Lumen ↓NO PI-3 kinase eNOS NADPH L-arginine O2 NO BH4 ↓NO Subendothelial Space Vasoconstriction

  20. EXERCISE IMPROVES ENDOTHELIAL FUNCTION Hamby et al, Diabetes Care 26:2119-2125, 2003 Watts, et al, Journal Pediatrics 144:620-625, 2004 Walsh, et al, JAP 95:20-25, 2003

  21. VASODILATION Eight weeks of training in healthy adults i Maeda, et al. Life Sciences 69:1005-1016, 2001

  22. Padilla, et al., European Journal of Applied Physiology, 98:256-262, 2006

  23. Padilla, et al. Medicine and Science in Sport and Exercise, in press.

  24. Fly, et al. Medicine and Science in Sport and Exercise, in press.

  25. Active & Inactive Overweight Men Treadmill Exercise FMD Response Harris, et al, Obesity, 2008

  26. Habitual Physical Activity Single Physical Activity Session Oxidative Source Antioxidant Defense (SOD) Anti-inflammatory Myokine ( IL-6)  Oxidative Stress ( 8 PG F2alpha) Inflammatory Stress ( TNF-alpha) Visceral Fat ( TNF-alpha) Insulin Resistance  NO bioavailability Systemic Inflammation ( CRP)  Blood Flow  Endothelial Function Insulin Resistance

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