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% V O 2 max; moderate, 50% V O 2 max; and high, 75% V O 2 max; 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 (7.5Ϯ2.4 to 11.4Ϯ5.8 mL/min per 100 mL tissue; PϽ0.05). 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-2Ј-deoxyguanosine (from 6.7Ϯ1.1 to 9.2Ϯ2.3 ng/mL; PϽ0.05) and serum concentrations of malondialdehyde-modified low-density lipoprotein (from 69.0Ϯ19.5 to 82.4Ϯ21.5 U/L; PϽ0.05), 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. (Circulation. 2003;108:530-535.)

Background-Patients with limb ischemia were associated with endothelial dysfunction. The purpose of this study was to determine whether autologous bone-marrow mononuclear cell (BM-MNC) implantation improves endothelial dysfunction in patients with limb ischemia. Methods and Results-We evaluated the leg blood flow (LBF) response to acetylcholine (ACh), an endotheliumdependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after BM-MNC implantation in 7 patients with limb ischemia. LBF was measured with a mercury-filled Silastic strain-gauge plethysmograph. The number of BM-MNCs implanted into ischemic limbs was 1.6ϫ10 9 Ϯ0.3ϫ10 9 . The number of CD34 ϩ cells included in the implanted BM-MNCs was 3.8ϫ10 7 Ϯ1.6ϫ10 7 . BM-MNC implantation improved the ankle-brachial pressure index (0.33Ϯ0.21 to 0.39Ϯ0.17, Pϭ0.06), transcutaneous oxygen pressure (28.4Ϯ11.5 to 36.6Ϯ5.2 mm Hg, Pϭ0.03), and pain-free walking time (0.8Ϯ0.6 to 2.9Ϯ2.2 minutes, Pϭ0.02). After BM-MNC implantation, LBF response to ACh was enhanced (19.3Ϯ6.8 versus 29.6Ϯ7.1 mL/min per 100 mL; Pϭ0.002). The vasodilatory effect of SNP was similar before and after BM-MNC implantation. Conclusions-These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.

These findings suggest that endothelium-dependent vasodilation is blunted through a decrease in NO release in non-dippers compared with patients who have dipper hypertension.

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