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

3. ↓NO NO eNOS L-arginine O 2 NADPH Lumen ↓NO BH 4 Subendothelial Space O2-O2- ONOO - O2-O2- Anti-Adhesion Anti- Coagulation Anti- Fibrolysis Vasodilation

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

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

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

17. 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: Relar Metab Disord 22:477-484, 1998. Caballero, A.E., Obesity Research 11:1278-1289, 2003. Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994. 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: Relar Metab Disord 22:477-484, 1998. Caballero, A.E., Obesity Research 11:1278-1289, 2003. Celermajer,et al. J Am Coll Cardiol 24:471-476, 1994.

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

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

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

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

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

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

24. NO L-arginine O 2 NADPH ↓NO Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasoconstriction Oxidative Stress O2-O2- ↓NO ONOO - O2-O2-

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

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

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

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

29. 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 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

32. NO L-arginine O 2 NADPH Lumen Subendothelial Space eNOS BH 4 PI-3 kinase Blood Flow Insulin Acetylcholine ↓NO Anti-Adhesion Anti-Coagulation Anti- Fibrolysis Vasoconstriction

33. 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 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 EXERCISE IMPROVES ENDOTHELIAL FUNCTION

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

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

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

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

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

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