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Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature.
- Source :
-
Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2018 Jan; Vol. 222 (1). Date of Electronic Publication: 2017 Jun 08. - Publication Year :
- 2018
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Abstract
- Aim: This study sought to determine the role of free radicals derived from mitochondria in the vasculature in the recognized age-related endothelial dysfunction of human skeletal muscle feed arteries (SMFAs).<br />Methods: A total of 44 SMFAs were studied with and without acute exposure to the mitochondria-targeted antioxidant MitoQ and nitric oxide synthase (NOS) blockade. The relative abundance of proteins from the electron transport chain, phosphorylated (p-) to endothelial (e) NOS ratio, manganese superoxide dismutase (MnSOD) and the mitochondria-derived superoxide (O2-) levels were assessed in SMFA. Endothelium-dependent and endothelium-independent SMFA vasodilation was assessed in response to flow-induced shear stress, acetylcholine (ACh) and sodium nitroprusside (SNP).<br />Results: MitoQ restored endothelium-dependent vasodilation in the old to that of the young when stimulated by both flow (young: 68 ± 5; old: 25 ± 7; old + MitoQ 65 ± 9%) and ACh (young: 97 ± 4; old: 59 ± 10; old + MitoQ: 98 ± 5%), but did not alter the initially uncompromised, endothelium-independent vasodilation (SNP). Compared to the young, MitoQ in the old diminished the initially elevated mitochondria-derived O2- levels and appeared to attenuate the breakdown of MnSOD. Furthermore, MitoQ increased the ratio of p-eNOS to NOS and the restoration of endothelium-dependent vasodilation in the old by MitoQ was ablated by NOS blockade.<br />Conclusion: This study demonstrated that MitoQ reverses age-related vascular dysfunction by what appears to be an NO-dependent mechanism in human SMFAs. These findings suggest that mitochondria-targeted antioxidants may have utility in terms of counteracting the attenuated blood flow and vascular dysfunction associated with advancing age.<br /> (© 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adult
Aged
Aging drug effects
Aging metabolism
Arteries drug effects
Arteries metabolism
Endothelium, Vascular pathology
Female
Humans
Male
Mitochondria metabolism
Muscle, Skeletal blood supply
Ubiquinone pharmacology
Vasodilation drug effects
Aging pathology
Antioxidants pharmacology
Arteries pathology
Endothelium, Vascular drug effects
Free Radicals metabolism
Organophosphorus Compounds pharmacology
Ubiquinone analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1748-1716
- Volume :
- 222
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Acta physiologica (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 28493603
- Full Text :
- https://doi.org/10.1111/apha.12893