Cutaneous blood flow during intradermal NO administration in young and older adults: roles for calcium-activated potassium channels and cyclooxygenase?
Cutaneous blood flow during intradermal NO administration in young and older adults: roles for calcium-activated potassium channels and cyclooxygenase?
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年轻人和老年人皮内 NO 给药期间的皮肤血流量：钙激活钾通道和环氧合酶的作用？
DOI：
10.1152/ajpregu.00041.2016
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Kenny,GlenP
中科院分区：
文献类型：
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作者：
Fujii,Naoto;Meade,RobertD;Minson,ChristopherT;Brunt,ViennaE;Boulay,Pierre;Sigal,RonaldJ;Kenny,GlenP
一氧化氮（NO）增加皮肤血流量;然而，基础机制仍有待阐明。我们假设，皮肤血流反应在皮内注射硝普钠（SNP，NO供体）的钙激活钾（KCa）通道和环氧合酶（考克斯）在年轻人的调节。我们还假设这些贡献在老年人中减少，因为衰老可以下调KCa通道并减少COX衍生的血管扩张剂前列腺素。在10名年轻（23 ± 5岁）和10名老年（54 ± 4岁）成人中，通过皮内微透析在4个前臂皮肤部位输注1）林格氏液（对照）、2）50 mM四乙基铵（TEA）（一种非特异性KCa通道阻滞剂）、3）10 mM酮咯酸（一种非特异性考克斯抑制剂）或4）50 mM TEA + 10 mM酮咯酸，测量皮肤血管传导性（CVC）。所有皮肤部位均用递增剂量的SNP（0.005、0.05、0.5、5和50 mM，各25 min）共输注。在SNP施用期间，CVC在酮咯酸位点处（0.005-50 mM，均P> 0.05）相对于对照相似，但在年轻成人中在TEA和TEA +酮咯酸位点处（0.005-0.05 mM，均P < 0.05）较低。在老年人中，在0.005-0.05 mM SNP给药期间，酮咯酸相对于对照增加了CVC（均P < 0.05），但当TEA共给药时未观察到这种增加（均P> 0.05）。此外，在老年人中，在任何浓度的SNP施用期间，单独TEA都不调节CVC（均P> 0.05）。我们表明，在低剂量NO给药期间（例如，0.005-0.05 mM），KCa通道有助于年轻人的皮肤血流调节;然而，在老年人中，考克斯抑制通过KCa通道依赖性机制增加皮肤血流。
Nitric oxide (NO) increases cutaneous blood flow; however, the underpinning mechanism(s) remains to be elucidated. We hypothesized that the cutaneous blood flow response during intradermal administration of sodium nitroprusside (SNP, a NO donor) is regulated by calcium-activated potassium (KCa) channels and cyclooxygenase (COX) in young adults. We also hypothesized that these contributions are diminished in older adults given that aging can downregulate KCa channels and reduce COX-derived vasodilator prostanoids. In 10 young (23 ± 5 yr) and 10 older (54 ± 4 yr) adults, cutaneous vascular conductance (CVC) was measured at four forearm skin sites infused with1) Ringer (Control),2) 50 mM tetraethylammonium (TEA), a nonspecific KCa channel blocker,3) 10 mM ketorolac, a nonspecific COX inhibitor, or4) 50 mM TEA + 10 mM ketorolac via intradermal microdialysis. All skin sites were coinfused with incremental doses of SNP (0.005, 0.05, 0.5, 5, and 50 mM each for 25 min). During SNP administration, CVC was similar at the ketorolac site (0.005–50 mM, allP> 0.05) relative to Control, but lower at the TEA and TEA + ketorolac sites (0.005–0.05 mM, allP< 0.05) in young adults. In older adults, ketorolac increased CVC relative to Control during 0.005–0.05 mM SNP administration (allP< 0.05), but this increase was not observed when TEA was coadministered (allP> 0.05). Furthermore, TEA alone did not modulate CVC during any concentration of SNP administration in older adults (allP> 0.05). We show that during low-dose NO administration (e.g., 0.005–0.05 mM), KCa channels contribute to cutaneous blood flow regulation in young adults; however, in older adults, COX inhibition increases cutaneous blood flow through a KCa channel-dependent mechanism.