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 V̇o_2peak (Y: 39.0 ± 3.8, O: 37.6 ± 3.1 mL·kg^-1·min^-1). Participants underwent graded local infusions of: the K⁺ channel activator Na₂S (10^-6 to 10^-1 M), acetylcholine (ACh, 10^-10 to 10^-1 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 (%CVC_max, 43°C+28 mM sodium nitroprusside). The %CVC_max response to Na₂S was higher in older adults (mean, O: 51.7 ± 3.9% vs. Y: 36.1 ± 5.3%; P = 0.03). %CVC_max was lower in the ACh+TEA vs. the ACh site starting at 10^-5 M (ACh: 34.0 ± 5.7% vs. ACh+TEA: 19.4 ± 4.5%; P = 0.002) in older and at 10^-4 M (ACh: 54.5 ± 9.4% vs. ACh+TEA: 31.2 ± 6.7%; P = 0.0002) in younger adults. %CVC_max was lower in the ACh+l-NAME vs. the ACh site in both groups starting at 10^-4 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.