The Influence of Healthy Aging on K+ Channel‐Dependent Microvascular Dilatory Function

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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.PURPOSETo evaluate the microvascular endothelial reliance on K+ channel‐mediated dilation with healthy aging.METHODSHealthy younger (n=6, 27±2 yrs, 23.4±0.5 kg/m2, 40.9±3.9 ml/kg/min) and older (n=9, 64±2 yrs, 23.7±1.1 kg/m2, 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 Na2S 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.RESULTSThere was a main effect of age (p<0.001), such that older adults had reduced overall %CVCmax 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%CVCmax vs. TEA: 13.2±4.1%CVCmax, p=0.0031), while differences were not observed in younger adults until 10−4 M (ACh: 51.5±5.0%CVCmax vs. TEA: 35.5±5.0%CVCmax, p=0.028). In response to Na2S, there was a main effect of age (p=0.032), with older adults showing overall higher %CVCmax compared to younger adults (older: 56.1±4.4%CVCmax vs. younger 38.8±5.7%CVCmax).CONCLUSIONSThese 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 InformationNIA T32‐AG049676