PMID- 32401629 OWN - NLM STAT- MEDLINE DCOM- 20201005 LR - 20240402 IS - 1522-1490 (Electronic) IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 319 IP - 1 DP - 2020 Jul 1 TI - Healthy active older adults have enhanced K(+) channel-dependent endothelial vasodilatory mechanisms. PG - R19-R25 LID - 10.1152/ajpregu.00049.2020 [doi] AB - 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 Na(2)S (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 degrees C+28 mM sodium nitroprusside). The %CVC(max) response to Na(2)S 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. FAU - Serviente, Corinna AU - Serviente C AD - Department of Kinesiology, Pennsylvania State University, University Park, Pennsylvania. AD - Center for Healthy Aging, Pennsylvania State University, University Park, Pennsylvania. FAU - Berry, Craig W AU - Berry CW AD - Department of Kinesiology, Pennsylvania State University, University Park, Pennsylvania. FAU - Kenney, W Larry AU - Kenney WL AD - Department of Kinesiology, Pennsylvania State University, University Park, Pennsylvania. AD - Center for Healthy Aging, Pennsylvania State University, University Park, Pennsylvania. FAU - Alexander, Lacy M AU - Alexander LM AD - Department of Kinesiology, Pennsylvania State University, University Park, Pennsylvania. AD - Center for Healthy Aging, Pennsylvania State University, University Park, Pennsylvania. LA - eng GR - R01 AG067471/AG/NIA NIH HHS/United States GR - R01 AG007004/AG/NIA NIH HHS/United States GR - T32-AG049676/AG/NIA NIH HHS/United States GR - R01 HL093238/HL/NHLBI NIH HHS/United States GR - UL1 TR002014/TR/NCATS NIH HHS/United States GR - UL1-TR002014/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200513 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Biological Factors) RN - 0 (Enzyme Inhibitors) RN - 0 (Potassium Channel Blockers) RN - 0 (Potassium Channels) RN - 0 (endothelium-dependent hyperpolarization factor) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Adult MH - Aged MH - Aging/physiology MH - Anaerobic Threshold/physiology MH - Biological Factors/physiology MH - Endothelium, Vascular/*physiology MH - Enzyme Inhibitors/pharmacology MH - Erythrocytes/drug effects/physiology MH - Female MH - Healthy Aging/*physiology MH - Humans MH - Male MH - Microcirculation MH - Middle Aged MH - NG-Nitroarginine Methyl Ester/pharmacology MH - Potassium Channel Blockers/pharmacology MH - Potassium Channels/agonists/*physiology MH - Regional Blood Flow/physiology MH - Vasodilation/*physiology PMC - PMC7468792 OTO - NOTNLM OT - aging OT - endothelium-derived hyperpolarizing factors OT - microvascular function OT - skin blood flow OT - vasodilation COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2020/05/14 06:00 MHDA- 2020/10/06 06:00 PMCR- 2021/07/01 CRDT- 2020/05/14 06:00 PHST- 2020/05/14 06:00 [pubmed] PHST- 2020/10/06 06:00 [medline] PHST- 2020/05/14 06:00 [entrez] PHST- 2021/07/01 00:00 [pmc-release] AID - R-00049-2020 [pii] AID - 10.1152/ajpregu.00049.2020 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2020 Jul 1;319(1):R19-R25. doi: 10.1152/ajpregu.00049.2020. Epub 2020 May 13.