Healthy active older adults have enhanced K+ channel-dependent endothelial vasodilatory mechanisms

Microvascular endothelial dysfunction, a precursor to atherosclerotic cardiovascular disease, increases with aging. Endothelium-derived hyperpolarizing factors (EDHFs), which act through K channels, regulate blood flow and are important to vascular health. It is unclear how EDHFs change with healthy aging. To evaluate microvascular endothelial reliance on K channel-mediated dilation as a function of age in healthy humans. Microvascular function was assessed using intradermal microdialysis in healthy younger (Y; n 7; 3 M/4 W; 26 1 yr) and older adults (O; n 12; 5 M/7 W; 64 2 yr) matched for V O2peak (Y: 39.0 3.8, O: 37.6 3.1 mL·kg1·min1). Participants underwent graded local infusions of: the K channel activator Na2S (106 to 101 M), acetylcholine (ACh, 1010 to 101 M), ACh the K channel inhibitor tetraethylammonium (TEA; 25 or 50 mM), and ACh the nitric oxide synthase-inhibitor L-NAME (15 mM). Red blood cell flux was measured with laser-Doppler flowmetry and used to calculate cutaneous vascular conductance (CVC; flux/mean arterial pressure) as a percentage of each site-specific maximum (%CVCmax, 43°C28 mM sodium nitroprusside). The %CVCmax response to Na2S was higher in older adults (mean, O: 51.7 3.9% vs. Y: 36.1 5.3%; P 0.03). %CVCmax was lower in the AChTEA vs. the ACh site starting at 105 M (ACh: 34.0 5.7% vs. AChTEA: 19.4 4.5%; P 0.002) in older and at 104 M (ACh: 54.5 9.4% vs. AChTEA: 31.2 6.7%; P 0.0002) in younger adults. %CVCmax was lower in the AChL-NAME vs. the ACh site in both groups starting at 104 M ACh (Y: P 0.001; O: P 0.02). Healthy active older adults have enhanced K channel-dependent endothelial vasodilatory mechanisms, suggesting increased responsiveness to EDHFs with age.