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(Hypertension. 2001;38:274.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Age-Related Reduction of NO Availability and Oxidative Stress in Humans
From the Department of Internal Medicine, University of Pisa, Pisa, Italy.
Correspondence to Stefano Taddei, MD, Department of Internal Medicine, University of Pisa, Via Roma 67, 56100 Pisa, Italy. E-mail s.taddei{at}int.med.unipi.itqq
Abstract— Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 µg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 µg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 100 µg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P<0.01) in hypertensive patients compared with control subjects. Moreover, in both groups, endothelium-dependent vasodilation declined with aging. In normotensive subjects, the inhibiting effect of L-NMMA on response to acetylcholine decreased in parallel with advancing age, whereas vitamin C increased vasodilation to acetylcholine in only the oldest group (age >60 years). In young hypertensive patients (age <30 years), vasodilation to acetylcholine was sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.
Key Words: endothelium • age • nitric oxide • oxidative stress • hypertension, essential
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C. Napoli, G. Aldini, J. L. Wallace, F. de Nigris, R. Maffei, P. Abete, D. Bonaduce, G. Condorelli, F. Rengo, V. Sica, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis PNAS, February 5, 2002; 99(3): 1689 - 1694. [Abstract] [Full Text] [PDF]
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