Slide 1

Slide 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

Slide 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

Slide 4

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

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

Slide 14

Slide 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 ++

Slide 16

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

Slide 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.

Slide 18

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

Slide 19

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

Slide 20

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

Slide 21

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

Slide 22

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

Slide 23

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

Slide 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-

Slide 25

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

Slide 26

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

Slide 27

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

Slide 28

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

Slide 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

Slide 30

Slide 31

Slide 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

Slide 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

Slide 34

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

Slide 35

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

Slide 36

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

Slide 37

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

Slide 38

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

Slide 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