Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin
Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin
复制标题
DOI：
10.1152/japplphysiol.01354.2011
复制
发表时间：
2012-06-01
影响因子：
3.3
通讯作者：
Holowatz, Lacy A.
中科院分区：
文献类型：
--
作者：
Bruning, Rebecca S.;Santhanam, Lakshmi;Holowatz, Lacy A.
Bruning RS，Santhanam L，Stanhewicz AE，Smith CJ，Berkowitz DE，肯尼WL，Holowatz LA.内皮型一氧化氮合酶在局部加热过程中介导皮肤血管舒张，并在中年人皮肤中减弱。J Appl Physiol 112：2019-2026，2012.首次发表于2012年4月12日; doi：10.1152/japplphysiol.01354.2011.-局部皮肤加热用于评估微血管功能在临床人群中，因为NO是所需的反应的充分表达，然而，存在争议的精确的NO合酶（NOS）亚型生产NO。人类衰老与衰减的皮肤血管舒张，但鲜为人知的是，中年人，用于与临床人群进行比较的年龄队列。我们假设内皮型一氧化氮合酶（eNOS）是介导局部加热过程中NO产生的主要亚型，并且eNOS依赖性血管舒张在中年皮肤中会减少。通过局部加热（42 ℃）和乙酰胆碱剂量反应（ACh-DR：0.01、0.1、1.0、5.0、10.0、50.0、100.0 mmol/l）方案诱导血管舒张。将四根微透析纤维置于24名男性和女性的皮肤中;年龄组为12名中年人（53 +/- 1岁）和12名年轻人（23 +/- 1岁）。部位作为对照，非选择性NOS抑制[N-G-硝基-L-精氨酸甲酯（L-NAME）]，诱导型NOS（iNOS）抑制（1400 W），神经元型NOS（nNOS）抑制（N-omega-丙基-L-精氨酸）。在局部热反应完全表达后，在所有部位灌注L-NAME。测量皮肤血管电导并标准化为最大值（%CVCmax：Nitropress）。与所有其他部位相比，L-NAME降低了基线、局部发热反应的所有阶段和所有ACh浓度下的%CVCmax。iNOS抑制降低了初始峰（53 +/- 2 vs. 60 +/- 2%CVCmax; P < 0.001）;然而，在局部加热或ACh-DR阶段，对照、nNOS-和iNOS-抑制位点之间没有其他差异。在中年皮肤中，ACh灌注（52 +/- 6 vs. 68 +/- 4%CVCmax; P = 0.013）和ACh灌注（50 mmol/l：83 +/- 3 vs. 93 +/- 2%CVCmax; 100 mmol/l：83 +/- 4 vs. 92 +/- 3%CVCmax;均P = 0.03）减少。各组皮肤活检组织中NOS同工酶的表达差异无统计学意义（均P > 0.05）。这些数据表明，eNOS介导的生产NO在局部加热和皮肤血管舒张衰减在中年皮肤。
Bruning RS, Santhanam L, Stanhewicz AE, Smith CJ, Berkowitz DE, Kenney WL, Holowatz LA. Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin. J Appl Physiol 112: 2019-2026, 2012. First published April 12, 2012; doi:10.1152/japplphysiol.01354.2011.-Local skin heating is used to assess microvascular function in clinical populations because NO is required for full expression of the response; however, controversy exists as to the precise NO synthase (NOS) isoform producing NO. Human aging is associated with attenuated cutaneous vasodilation but little is known about the middle aged, an age cohort used for comparison with clinical populations. We hypothesized that endothelial NOS (eNOS) is the primary isoform mediating NO production during local heating, and eNOS-dependent vasodilation would be reduced in middle-aged skin. Vasodilation was induced by local heating (42 degrees C) and during acetylcholine dose-response (ACh-DR: 0.01, 0.1, 1.0, 5.0, 10.0, 50.0, 100.0 mmol/l) protocols. Four microdialysis fibers were placed in the skin of 24 men and women; age cohorts were 12 middle-aged (53 +/- 1 yr) and 12 young (23 +/- 1 yr). Sites served as control, nonselective NOS inhibited [N-G-nitro-L-arginine methyl ester (L-NAME)], inducible NOS (iNOS) inhibited (1400W), and neuronal NOS (nNOS) inhibited (N-omega-propyl-L-arginine). After full expression of the local heating response, L-NAME was perfused at all sites. Cutaneous vascular conductance was measured and normalized to maximum (%CVCmax: Nitropress). L-NAME reduced %CVCmax at baseline, all phases of the local heating response, and at all ACh concentrations compared with all other sites. iNOS inhibition reduced the initial peak (53 +/- 2 vs. 60 +/- 2%CVCmax; P < 0.001); however, there were no other differences between control, nNOS-, and iNOS-inhibited sites during the phases of local heating or ACh-DR. When age cohorts were compared, NO-dependent vasodilation during local heating (52 +/- 6 vs. 68 +/- 4%CVCmax; P = 0.013) and ACh perfusion (50 mmol/l: 83 +/- 3 vs. 93 +/- 2%CVCmax; 100 mmol/l: 83 +/- 4 vs. 92 +/- 3%CVCmax; both P = 0.03) were reduced in middle-aged skin. There were no differences in NOS isoform expression obtained from skin biopsy samples between groups (all P > 0.05). These data suggest that eNOS mediates the production of NO during local heating and that cutaneous vasodilation is attenuated in middle-aged skin.