Cutaneous neuronal nitric oxide is specifically decreased in postural tachycardia syndrome.
Cutaneous neuronal nitric oxide is specifically decreased in postural tachycardia syndrome.
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皮肤神经元一氧化氮在体位性心动过速综合征中特别减少。
DOI：
10.1152/ajpheart.00600.2007
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Taneja,Indu
中科院分区：
文献类型：
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作者：
Stewart,JulianM;Medow,MarvinS;Minson,ChristopherT;Taneja,Indu
低流量体位性心动过速综合征（POTS）与一氧化氮（NO）活性降低有关，推测其来源于内皮细胞。我们测试的假设，皮肤微血管神经元NO（nNO）受损，而不是内皮NO（eNO），在POTS。我们对年龄为22.5 ± 2岁的受试者进行了三组实验。我们用激光多普勒血流仪反应顺序增加乙酰胆碱（ACh）剂量和小牛局部皮肤加热反应作为NO的生物测定。在局部加热过程中，我们表明，当选择性神经元nNO合酶（nNOS）的底物N ω-硝基-l-精氨酸-2，4-l-二氨基丁酰胺（N ω，10 mM）通过皮内微透析递送，皮肤血管传导性（CVC）降低的量相当于非选择性NO合酶（NOS）抑制剂硝基-l-精氨酸（NLA，10 mM）。我们证明，使用N ω阻断nNOS对ACh的反应减弱最小，但NLA明显减弱，表明eNO主要由ACh受体介导的NO释放组成。我们进一步证明，ACh的剂量反应是最低限度地减少，而局部热介导的NO依赖性反应显着减少POTS与对照组相比。这与POTS中完整的内皮功能和神经元来源的NO减少是一致的。与对照组（90 ± 4% CVCmax）相比，POTS中的局部加热反应高度减弱[60 ± 6%最大CVC（% CVCmax）]，但平台反应降低至与nNOS抑制相同的水平（50 ± 3% CVCmax与47 ± 2% CVCmax相比），表明POTS患者中nNO生物利用度降低。这些数据表明，nNO活性，但不是NO的内皮NOS的起源是减少在低流量POTS。
Low flow postural tachycardia syndrome (POTS), is associated with reduced nitric oxide (NO) activity assumed to be of endothelial origin. We tested the hypothesis that cutaneous microvascular neuronal NO (nNO) is impaired, rather than endothelial NO (eNO), in POTS. We performed three sets of experiments on subjects aged 22.5 ± 2 yr. We used laser-Doppler flowmetry response to sequentially increase acetylcholine (ACh) doses and the local cutaneous heating response of the calf as bioassays for NO. During local heating we showed that when the selective neuronal nNO synthase (nNOS) inhibitorNω-nitro-l-arginine-2,4-l-diaminobutyric amide (Nω, 10 mM) was delivered by intradermal microdialysis, cutaneous vascular conductance (CVC) decreased by an amount equivalent to the largest reduction produced by the nonselective NO synthase (NOS) inhibitor nitro-l-arginine (NLA, 10 mM). We demonstrated that the response to ACh was minimally attenuated by nNOS blockade usingNωbut markedly attenuated by NLA, indicating that eNO largely comprises the receptor-mediated NO release by ACh. We further demonstrated that the ACh dose response was minimally reduced, whereas local heat-mediated NO-dependent responses were markedly reduced in POTS compared with control subjects. This is consistent with intact endothelial function and reduced NO of neuronal origin in POTS. The local heating response was highly attenuated in POTS [60 ± 6 percent maximum CVC(%CVCmax)] compared with control (90 ± 4 %CVCmax), but the plateau response decreased to the same level with nNOS inhibition (50 ± 3 %CVCmaxin POTS compared with 47 ± 2 %CVCmax), indicating reduced nNO bioavailability in POTS patients. The data suggest that nNO activity but not NO of endothelial NOS origin is reduced in low-flow POTS.