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Mitochondrial respiratory function in the vasculature with advancing age: Examining the link to vasodilatory dysfunction.
Author(s) -
Park Soung Hun,
Kwon Oh Sung,
park SongYoung,
Andtbacka Robert H. I.,
Hyngstrom John R.,
Richardson Russell S.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.578.2
Subject(s) - vasodilation , sodium nitroprusside , respiration , medicine , respiratory system , endocrinology , acetylcholine , endothelium , endothelial dysfunction , chemistry , anatomy , nitric oxide
Background Unlike cardiac and skeletal muscle, the role of mitochondria in the vasculature is still unclear. Therefore, this study sought to document mitochondrial respiratory function in the vasculature with advancing age and examine the link to age‐related vasodilatory dysfunction. Methods Skeletal muscle feed arteries (SMFAs) were harvested from young (30±6yrs, n=4) and old (69±8yrs, n=20) subjects. Mitochondrial respiratory function was assessed in permeablized smooth muscle fibers and vasodilation in SMFAs was assessed in response to flow‐induced shear stress, acetylcholine (ACh), and sodium nitroprusside (SNP). Results Complex I+II, state 3 respiration was significantly lower in the old (young: 12.13±0.48, old: 8.41±0.68 pmol/s/mg), while state 4 was significantly higher in the old (young: 4.69±0.2, old: 7.59±0.67 pmol/s/mg). The respiratory control ratio (RCR), state 3/state 4 respiration, was also significantly attenuated in the old (young: 2.6±0.17, old: 1.19±0.09). Endothelium‐dependent vasodilation was attenuated in the old whether induced by flow (young: 103±6, old: 46±5 %; P <0.01) or ACh (young: 110±12, old: 53±4 %; P <0.01), while endothelial‐independent vasodilation was not altered by age. Thus, there was significant correlation between state 3 respiration and flow‐mediated ( r =0.61, P <0.01) and ACh‐dependent vasodilation ( r =0.62, P <0.01), but not with the SNP‐dependent response. State 4 respiration was negatively correlated only with ACh‐dependent vasodilation ( r =−0.45, P <0.05). RCR also exhibited a strong positive correlation with flow‐mediated ( r =0.77, P <0.001) and ACh‐dependent vasodilation ( r =0.81, P <0.001), but not the SNP‐dependent response. Conclusions Advancing age results in altered mitochondrial respiratory capacity and these changes in mitochondrial function are strongly linked to age‐related endothelial dysfunction in SMFAs. Support or Funding Information The National Heart, Lung, and Blood Institute at the National Institute of Health (PO1 HL1091830) and the Veteran's Administration Rehabilitation Research and Development Service (E6910‐R, E1697‐R, E1433‐P, E9275‐L and E1572‐P). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .