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The Influence of Healthy Aging on K + Channel‐Dependent Microvascular Dilatory Function
Author(s) -
Serviente Corinna,
Berry Craig,
Kenney W. Larry,
Alexander Lacy M.
Publication year - 2020
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.2020.34.s1.02888
Subject(s) - endothelial dysfunction , medicine , vasodilation , sodium nitroprusside , nitric oxide , cardiology , endothelium , microdialysis , endocrinology , central nervous system
Aging is associated with reduced microvascular endothelial function, contributing to increased cardiovascular disease risk. Microvascular dysfunction is usually measured by evaluating endothelial nitric oxide‐dependent vasodilation. However, other vascular signaling pathways, including endothelial derived hyperpolarizing factors (EDHFs), acting through K + channels, are also important for maintenance of vascular health and may be influenced by age and disease. It remains unclear how microvascular EDHFs are affected by healthy aging. PURPOSE To evaluate the microvascular endothelial reliance on K + channel‐mediated dilation with healthy aging. METHODS Healthy younger (n=6, 27±2 yrs, 23.4±0.5 kg/m 2 , 40.9±3.9 ml/kg/min) and older (n=9, 64±2 yrs, 23.7±1.1 kg/m 2 , 37.5±4.0 ml/kg/min) men and women (younger: 3M/3W, older: 3M/6W) underwent graded infusions of the endothelial dependent agonist acetylcholine (ACh, 10 −6 to 10 −2 M) alone and in combination with the K + channel blocker tetraethylammonium (TEA, 25 mM) via cutaneous intradermal microdialysis. Additionally, responses to graded infusions (20mM to 100mM) of the K + channel activator Na 2 S were evaluated (older, n=10). Red blood cell flux was measured at each site using laser Doppler flowmetry. Cutaneous vascular conductance (CVC: flux/mean arterial pressure) was calculated as a percentage of site specific maximum (43°C + 28mM sodium nitroprusside). Data are presented as mean ± SEM. RESULTS There was a main effect of age (p<0.001), such that older adults had reduced overall %CVC max compared to younger adults. There was an interaction between site treatment and age (p<0.001). Within older adults, blood flow was lower in the TEA vs. the ACh site starting at 10 −5 M (ACh: 31.8±4.1%CVC max vs. TEA: 13.2±4.1%CVC max , p=0.0031), while differences were not observed in younger adults until 10 −4 M (ACh: 51.5±5.0%CVC max vs. TEA: 35.5±5.0%CVC max , p=0.028). In response to Na 2 S, there was a main effect of age (p=0.032), with older adults showing overall higher %CVC max compared to younger adults (older: 56.1±4.4%CVC max vs. younger 38.8±5.7%CVC max ). CONCLUSIONS These data suggest that heathy older adults have increased reliance on K + channel‐dependent endothelial dilatory mechanisms compared to younger adults, suggesting increased reliance on EDHFs with healthy age. Support or Funding Information NIA T32‐AG049676