↑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.

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Presentation transcript:

↑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

↓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

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

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

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

Faulx, et al, American Heart Journal 145: , 2003 Iiyama, et al. American Heart Journal 132: , 1996 Hashimoto, et al. International Journal of Obesity: Relar Metab Disord 22: , Caballero, A.E., Obesity Research 11: , Celermajer,et al. J Am Coll Cardiol 24: , Faulx, et al, American Heart Journal 145: , 2003 Iiyama, et al. American Heart Journal 132: , 1996 Hashimoto, et al. International Journal of Obesity: Relar Metab Disord 22: , Caballero, A.E., Obesity Research 11: , Celermajer,et al. J Am Coll Cardiol 24: , 1994.

Hasimoto, et al. Circulation 92: , Apparently Healthy

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

Celermajer,et al. J Am Coll Cardiol 24: , Aging

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

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

Caballero, A.E., Obesity Research 11: , Diabetes

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-

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

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

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

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

Tsai, et al. Clinical Science 106: , 2004 Anderson, et al, Atherosclerosis 154: , 2001 Ceriello, et al, Circulation 106: , 2002 Tsai, et al. Clinical Science 106: , 2004 Anderson, et al, Atherosclerosis 154: , 2001 Ceriello, et al, Circulation 106: , 2002

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

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

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

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

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

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

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

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