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(Circulation. 2003;108:530.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Effect of Different Intensities of Exercise on Endothelium-Dependent Vasodilation in Humans

Role of Endothelium-Dependent Nitric Oxide and Oxidative Stress

Chikara Goto, RPT, MS; Yukihito Higashi, MD, PhD; Masashi Kimura, MD; Kensuke Noma, MD; Keiko Hara, MD; Keigo Nakagawa, MD; Mitsutoshi Kawamura, RPT, MS; Kazuaki Chayama, MD, PhD; Masao Yoshizumi, MD, PhD; Isao Nara, RPT, PhD

From the Program in Physical Therapy Health Sciences, School of Medicine (C.G., M.K., I.N.), Department of Cardiovascular Physiology and Medicine (Y.H., M.Y.), Department of Medicine and Molecular Science (K. Noma, M.K., K.H., K. Nakagawa, K.C.), Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

Correspondence to Yukihito Higashi, MD, PhD, FAHA, Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail yhigashi{at}hiroshima-u.ac.jp

Received June 11, 2002; de novo received February 19, 2003; revision received May 5, 2003; accepted May 5, 2003.

Background— Aerobic exercise enhances endothelium-dependent vasodilation in hypertensive patients, patients with chronic heart failure, and healthy individuals. However, it is unclear how the intensity of exercise affects endothelial function in humans. The purpose of the present study was to determine the effects of different intensities of exercise on endothelium-dependent vasodilation in humans.

Methods and Results— We evaluated the forearm blood flow responses to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after different intensities of exercise (mild, 25% O₂max; moderate, 50% O₂max; and high, 75% O₂max; bicycle ergometers, 30 minutes, 5 to 7 times per week for 12 weeks) in 26 healthy young men. Forearm blood flow was measured using a mercury-filled Silastic strain-gauge plethysmograph. Twelve weeks of moderate-intensity exercise, but not mild- or high-intensity exercise, significantly augmented acetylcholine-induced vasodilation (7.5±2.4 to 11.4±5.8 mL/min per 100 mL tissue; P<0.05). No intensity of aerobic exercise altered isosorbide dinitrate–induced vasodilation. The administration of N^G-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished the moderate-intensity exercise-induced augmentation of the forearm blood flow response to acetylcholine. High-intensity exercise increases plasma concentrations of 8-hydroxy-2'-deoxyguanosine (from 6.7±1.1 to 9.2±2.3 ng/mL; P<0.05) and serum concentrations of malondialdehyde-modified low-density lipoprotein (from 69.0±19.5 to 82.4±21.5 U/L; P<0.05), whereas moderate exercise tended to decrease both indices of oxidative stress.

Conclusions— These findings suggest that moderate-intensity aerobic exercise augments endothelium-dependent vasodilation in humans through the increased production of nitric oxide and that high-intensity exercise possibly increases oxidative stress.

Key Words: endothelium • exercise • nitric oxide • free radicals • blood flow

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