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Circulation. 1999;100:1194-1202

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(Circulation. 1999;100:1194-1202.)
© 1999 American Heart Association, Inc.


Clinical Investigation and Reports

Regular Aerobic Exercise Augments Endothelium-Dependent Vascular Relaxation in Normotensive As Well As Hypertensive Subjects

Role of Endothelium-Derived Nitric Oxide

Yukihito Higashi, MD, PhD; Shota Sasaki, MD; Satoshi Kurisu, MD; Atsunori Yoshimizu, MD; Nobuo Sasaki, MD; Hideo Matsuura, MD, PhD; Goro Kajiyama, MD, PhD; Tetsuya Oshima, MD, PhD

From the First Department of Internal Medicine (Y.H., S.S., S.K., A.Y., N.S., H.M., G.K.) and the Department of Clinical Laboratory Medicine (T.O.), Hiroshima University School of Medicine, Japan.

Correspondence to Yukihito Higashi, MD, PhD, Hiroshima University School of Medicine, First Department of Internal Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail yhigashi{at}mcai.med.hiroshima-u.ac.jp

Background—Several nonpharmacological interventions, including exercise, are recommended in primary prevention of hypertension and other cardiovascular diseases in which the pathogenetic role of endothelial dysfunction has been suggested. We studied the effects of long-term aerobic exercise on endothelial function in patients with essential hypertension.

Methods and Results—The forearm blood flow was measured by strain-gauge plethysmography. The responses of forearm vasculature to acetylcholine were smaller in the hypertensive patients than in the normotensive subjects. There was no significant difference in forearm vascular responses to isosorbide dinitrate in the normotensive and hypertensive subjects. We evaluated the effects of physical exercise for 12 weeks on forearm hemodynamics in untreated patients with mild essential hypertension who were divided randomly into an exercise group (n=10) and a control group (n=7). After 12 weeks, the forearm blood flow response to acetylcholine increased significantly, from 25.8±9.8 to 32.3±11.2 mL · min-1 · 100 mL tissue-1 (P<0.05), in the exercise group but not in the control group. The increase in the forearm blood flow after isosorbide dinitrate was similar before and after 12 weeks of follow-up in both groups. The infusion of NG-monomethyl-L-arginine abolished the exercise-induced enhancement of forearm vasorelaxation evoked by acetylcholine in the exercising group. In normotensive subjects also, long-term aerobic exercise augmented acetylcholine-stimulated nitric oxide release.

Conclusions—These findings suggest that long-term physical exercise improves endothelium-dependent vasorelaxation through an increase in the release of nitric oxide in normotensive as well as hypertensive subjects.


Key Words: exercise • nitric oxide • acetylcholine • endothelium • hypertension




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