一氧化氮合酶和活性氧在TRPA1介导的年轻人和老年人皮肤血管舒张中的作用。

Involvement of nitric oxide synthase and reactive oxygen species in TRPA1-mediated cutaneous vasodilation in young and older adults.

作者信息

McGarr Gregory W, King Kelli E, Cassan Casey J M, Janetos Kristina-Marie T, Fujii Naoto, Kenny Glen P

机构信息

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada.

Human and Environmental Physiology Research Unit, School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada; Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba, Tsukuba City, Japan; Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Japan.

出版信息

Microvasc Res. 2023 Jan;145:104443. doi: 10.1016/j.mvr.2022.104443. Epub 2022 Oct 5.

DOI:10.1016/j.mvr.2022.104443

PMID:36208670

Abstract

OBJECTIVE

To investigate the nitric oxide synthase (NOS) and reactive oxygen species (ROS) contributions of the cutaneous vasodilator response to transient receptor potential ankyrin-1 channel (TRPA1) activation in young and older adults.

MATERIALS AND METHODS

In sixteen young (20 ± 2 years, 8 females) and sixteen older adults (61 ± 5 years, 8 females), cutaneous vascular conductance normalized to maximum vasodilation (%CVC) was assessed at four dorsal forearm skin sites continuously perfused via microdialysis with: 1) vehicle solution (Control, 2 % dimethyl sulfoxide, 2 % Ringer, 96 % propylene glycol), 2) 10 mM Ascorbate (non-specific ROS inhibitor), 3) 10 mM L-NAME (non-specific NOS inhibitor), or 4) Ascorbate+L-NAME. The TRPA1 agonist cinnamaldehyde was co-administered at all sites [0 % (baseline), 2.9 %, 8.8 %, 26.4 %; ≥ 30 min per dose].

RESULTS

%CVC was not different between groups for Control, L-NAME, and Ascorbate (all p > 0.05). However, there were significant main dose effects for each site wherein %CVC was greater than baseline from 2.9 % to 26.4 % cinnamaldehyde for Control and Ascorbate, and at 26.4 % cinnamaldehyde for L-NAME and Ascorbate+L-NAME (all p < 0.05). For Ascorbate+L-NAME, there was a significant main group effect, wherein perfusion was 6 %CVC [95% CI: 2, 11, p < 0.05] greater in the older compared to the young group across all cinnamaldehyde doses. There was a significant main site effect for area under the curve wherein L-NAME and Ascorbate+L-NAME were lower than Control and Ascorbate across groups (all p < 0.05).

CONCLUSION

The NOS-dependent cutaneous vasodilator response to TRPA1 activation is maintained in older adults, with no detectable contribution of ascorbate-sensitive ROS in either age group.

摘要

目的

研究一氧化氮合酶（NOS）和活性氧（ROS）在年轻人和老年人皮肤血管舒张反应中对瞬时受体电位锚蛋白1通道（TRPA1）激活的作用。

材料与方法

选取16名年轻人（20±2岁，8名女性）和16名老年人（61±5岁，8名女性），通过微透析在四个前臂背侧皮肤部位连续灌注以下溶液，评估归一化至最大血管舒张的皮肤血管传导率（%CVC）：1）溶媒溶液（对照，2%二甲亚砜、2%林格氏液、96%丙二醇），2）10 mM抗坏血酸（非特异性ROS抑制剂），3）10 mM L-硝基精氨酸甲酯（非特异性NOS抑制剂），或4）抗坏血酸+L-硝基精氨酸甲酯。在所有部位共同给予TRPA1激动剂肉桂醛[0%（基线）、2.9%、8.8%、26.4%；每剂≥30分钟]。

结果

对照组、L-硝基精氨酸甲酯组和抗坏血酸组之间的%CVC在两组间无差异（所有p>0.05）。然而，每个部位均存在显著的主要剂量效应，其中对照组和抗坏血酸组在肉桂醛浓度从2.9%至26.4%时，%CVC高于基线，L-硝基精氨酸甲酯组和抗坏血酸+L-硝基精氨酸甲酯组在肉桂醛浓度为26.4%时，%CVC高于基线（所有p<0.05）。对于抗坏血酸+L-硝基精氨酸甲酯组，存在显著的主要组间效应，即在所有肉桂醛剂量下，老年人组的灌注比年轻人组高6%CVC[95%CI：2, 11, p<0.05]。曲线下面积存在显著的主要部位效应，即L-硝基精氨酸甲酯组和抗坏血酸+L-硝基精氨酸甲酯组在各年龄组中均低于对照组和抗坏血酸组（所有p<0.05）。