Black Mark A, Green Daniel J, Cable N Timothy
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, 12-21 Webster Street, Liverpool L3 2ET, UK.
J Physiol. 2008 Jul 15;586(14):3511-24. doi: 10.1113/jphysiol.2008.153742. Epub 2008 May 15.
Ageing is associated with impaired endothelium-derived nitric oxide (NO) function in human microvessels. We investigated the impact of cardiorespiratory fitness and exercise training on physiological and pharmacological NO-mediated microvascular responses in older subjects. NO-mediated vasodilatation was examined in young, older sedentary and older fit subjects who had two microdialysis fibres embedded into the skin on the ventral aspect of the forearm and laser Doppler probes placed over these sites. Both sites were then heated to 42 degrees C, with Ringer solution infused in one probe and N-nitro-L-arginine methyl ester (L-NAME) through the second. In another study, three doses of ACh were infused in the presence or absence of L-NAME in similar subjects. The older sedentary subjects then undertook exercise training, with repeat studies at 12 and 24 weeks. The NO component of the heat-induced rise in cutaneous vascular conductance (CVC) was diminished in the older sedentary subjects after 30 min of prolonged heating at 42 degrees C (26.9 +/- 3.9%CVC(max)), compared to older fit (46.2 +/- 7.0%CVC(max), P < 0.05) and young subjects (41.2 +/- 5.2%CVC(max), P < 0.05), whereas exercise training in the older sedentary group enhanced NO-vasodilator function in response to incremental heating (P < 0.05). Similarly, the NO contribution to ACh responses was impaired in the older sedentary versus older fit subjects (low dose 3.2 +/- 1.3 versus 6.6 +/- 1.3%CVC(max); mid dose 11.4 +/- 2.4 versus 21.6 +/- 4.5%CVC(max); high dose 35.2 +/- 6.0 versus 52.6 +/- 7.9%CVC(max), P < 0.05) and training reversed this (12 weeks: 13.7 +/- 3.6, 28.9 +/- 5.3, 56.1 +/- 3.9%CVC(max), P < 0.05). These findings indicate that maintaining a high level of fitness, or undertaking exercise training, prevents age-related decline in indices of physiological and pharmacological microvascular NO-mediated vasodilator function. Since higher levels of NO confer anti-atherogenic benefit, this study has potential implications for the prevention of microvascular dysfunction in humans.
衰老与人体微血管中内皮源性一氧化氮（NO）功能受损有关。我们研究了心肺适能和运动训练对老年受试者生理和药理学上NO介导的微血管反应的影响。在年轻、老年久坐不动和老年健康受试者中检测了NO介导的血管舒张功能，这些受试者在前臂腹侧皮肤中植入了两根微透析纤维，并在这些部位放置了激光多普勒探头。然后将两个部位都加热到42摄氏度，在一个探头中注入林格溶液，通过第二个探头注入N-硝基-L-精氨酸甲酯（L-NAME）。在另一项研究中，在类似的受试者中，在有或没有L-NAME的情况下注入三种剂量的乙酰胆碱（ACh）。然后，老年久坐不动的受试者进行运动训练，并在12周和24周时重复进行研究。在42摄氏度下长时间加热30分钟后，老年久坐不动的受试者中，热诱导的皮肤血管传导率（CVC）升高的NO成分减少（26.9±3.9%CVC（最大值）），相比之下，老年健康受试者（46.2±7.0%CVC（最大值），P<0.05）和年轻受试者（41.2±5.2%CVC（最大值），P<0.05），而老年久坐不动组的运动训练增强了对递增加热的NO血管舒张功能（P<0.05）。同样，与老年健康受试者相比，老年久坐不动的受试者中，NO对ACh反应的贡献受损（低剂量3.2±1.3与6.6±1.3%CVC（最大值）；中剂量11.4±2.4与21.6±4.5%CVC（最大值）；高剂量35.2±6.0与52.6±7.9%CVC（最大值），P<0.05），而训练逆转了这种情况（12周时：13.7±3.6、28.9±5.3、56.1±3.9%CVC（最大值），P<0.05）。这些发现表明，保持高水平的适能或进行运动训练可预防与年龄相关的生理和药理学微血管NO介导的血管舒张功能指标的下降。由于较高水平的NO具有抗动脉粥样硬化益处，本研究对预防人类微血管功能障碍具有潜在意义。
