Author ORCID Identifier
Document Type
Article
Publication Date
5-11-2017
Publication Title
Acta Physiologica
Volume
222
Issue
1
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).
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 () 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).
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 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.
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.
Recommended Citation
Park, S.-.-Y., Kwon, O.S., Andtbacka, R.H.I., Hyngstrom, J.R., Reese, V., Murphy, M.P. and Richardson, R.S. (2018), Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature. Acta Physiol, 222: e12893. https://doi.org/10.1111/apha.12893
Comments
"This is the peer reviewed version of the following article: Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature. Acta Physiol, 222: e12893, which has been published in final form at https://doi.org/10.1111/apha.12893. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited."