Age-Related Reduction of NO Availability and Oxidative Stress in Humans
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 N G -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.
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Reduced nitric oxide bioavailability due to decreased endothelial nitric oxide synthase production, increased degradation, or both is the key mechanism mediating vascular endothelial dysfunction with aging.
“Reduced bioavailability of NO as a result of decreased production by endothelial NO synthase (eNOS), increased degradation, or both, also is the key mechanism mediating vascular endothelial dysfunction with aging (118, 164, 177).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [177]
The key mechanism for reduced nitric oxide bioavailability with aging is oxidative stress.
“The key mechanism for reduced NO bioavailability with aging is oxidative stress (49, 164, 177).”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [177]
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- Authors
- Taddei, S., Virdis, A., Ghiadoni, L., Salvetti, G., Bernini, G., Magagna, A., & Salvetti, A.
- Affiliations
- University of Pisa (IT)
- Venue
- Hypertension
- Published
- 2001-08
- Volume
- 38
- Issue
- 2
- Pages
- 274-279
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2100312221
- Cited by
- 664
- References
- 30
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 14 · 2023: 18 · 2022: 26 · 2021: 33 · 2020: 23 · 2019: 23 · 2018: 35 · 2017: 31 · 2016: 38 · 2015: 41 · 2014: 35 · 2013: 32 · 2012: 39
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- endothelial dysfunction, aging, nitric oxide, oxidative stress, essential hypertension, endothelium-dependent vasodilation, acetylcholine, sodium nitroprusside, L-NMMA, vitamin C, forearm blood flow
- MeSH terms
- Acetylcholine, Adult, Age Factors, Aged, Ascorbic Acid, Drug Antagonism, Endothelium, Vascular, Enzyme Inhibitors, Female, Forearm, Humans, Hypertension, Male, Middle Aged, Nitric Oxide, Nitroprusside, Regional Blood Flow, Vasodilation, Vasodilator Agents, Oxidative Stress, Nitric Oxide Synthase, omega-N-Methylarginine
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