Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Salt Lake City, Utah.
Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
Am J Physiol Heart Circ Physiol. 2021 Feb 1;320(2):H668-H678. doi: 10.1152/ajpheart.00784.2020. Epub 2020 Dec 11.
Passive leg movement (PLM) evokes a robust and predominantly nitric oxide (NO)-mediated increase in blood flow that declines with age and disease. Consequently, PLM is becoming increasingly accepted as a sensitive assessment of endothelium-mediated vascular function. However, a substantial PLM-induced hyperemic response is still evoked despite nitric oxide synthase (NOS) inhibition. Therefore, in nine young healthy men (25 ± 4 yr), this investigation aimed to determine whether the combination of two potent endothelium-dependent vasodilators, specifically prostaglandin (PG) and endothelium-derived hyperpolarizing factor (EDHF), account for the remaining hyperemic response to the two variants of PLM, PLM (60 movements) and single PLM (sPLM, 1 movement), when NOS is inhibited. The leg blood flow (LBF, Doppler ultrasound) response to PLM and sPLM following the intra-arterial infusion of -monomethyl-l-arginine (l-NMMA), to inhibit NOS, was compared to the combined inhibition of NOS, cyclooxygenase (COX), and cytochrome -450 (CYP450) by l-NMMA, ketorolac tromethamine (KET), and fluconazole (FLUC), respectively. NOS inhibition attenuated the overall LBF [area under the curve (LBF)] response to both PLM (control: 456 ± 194, l-NMMA: 168 ± 127 mL, < 0.01) and sPLM (control: 185 ± 171, l-NMMA: 62 ± 31 mL, = 0.03). The combined inhibition of NOS, COX, and CYP450 (i.e., l-NMMA+KET+FLUC) did not further attenuate the hyperemic responses to PLM (LBF: 271 ± 97 mL, > 0.05) or sPLM (LBF: 72 ± 45 mL, > 0.05). Therefore, PG and EDHF do not collectively contribute to the non-NOS-derived NO-mediated, endothelium-dependent hyperemic response to either PLM or sPLM in healthy young men. These findings add to the mounting evidence and understanding of the vasodilatory pathways assessed by the PLM and sPLM vascular function tests. Passive leg movement (PLM) evokes a highly nitric oxide (NO)-mediated hyperemic response and may provide a novel evaluation of vascular function. The contributions of endothelium-dependent vasodilatory pathways, beyond NO and including prostaglandins and endothelium-derived hyperpolarizing factor, to the PLM-induced hyperemic response to PLM have not been evaluated. With intra-arterial drug infusion, the combined inhibition of nitric oxide synthase (NOS), cyclooxygenase, and cytochrome -450 (CYP450) pathways did not further diminish the hyperemic response to PLM compared with NOS inhibition alone.
被动腿部运动（PLM）会引起强烈的、主要由一氧化氮（NO）介导的血流增加，这种增加会随着年龄的增长和疾病的发生而下降。因此，PLM 正越来越被认为是一种评估内皮介导的血管功能的敏感方法。然而，尽管抑制了一氧化氮合酶（NOS），仍然会引起相当大的 PLM 诱导的充血反应。因此，在 9 名年轻健康男性（25±4 岁）中，本研究旨在确定两种强效的内皮依赖性血管扩张剂，即前列腺素（PG）和内皮衍生的超极化因子（EDHF），是否可以解释在 NOS 被抑制时，PLM 的两种变体（PLM（60 次运动）和单次 PLM（sPLM，1 次运动））的剩余充血反应。在经动脉内输注 -单甲基-l-精氨酸（l-NMMA）抑制 NOS 后，比较 PLM 和 sPLM 的腿部血流（Doppler 超声）反应与 NOS、环氧化酶（COX）和细胞色素 P450（CYP450）的联合抑制，分别为 l-NMMA、酮咯酸氨丁三醇（KET）和氟康唑（FLUC）。NOS 抑制减弱了两种 PLM（对照组：456±194，l-NMMA：168±127mL， < 0.01）和 sPLM（对照组：185±171，l-NMMA：62±31mL， = 0.03）的总体 LBF[曲线下面积（LBF）]反应。NOS、COX 和 CYP450 的联合抑制（即 l-NMMA+KET+FLUC）并未进一步减弱 PLM（LBF：271±97mL， > 0.05）或 sPLM（LBF：72±45mL， > 0.05）的充血反应。因此，PG 和 EDHF 并没有共同导致健康年轻男性中 PLM 或 sPLM 的非 NOS 衍生的、NO 介导的内皮依赖性充血反应。这些发现增加了对 PLM 和 sPLM 血管功能测试评估的血管舒张途径的越来越多的证据和理解。被动腿部运动（PLM）引起强烈的一氧化氮（NO）介导的充血反应，可能为血管功能提供新的评估。NO 以外的内皮依赖性血管舒张途径，包括前列腺素和内皮衍生的超极化因子，对 PLM 诱导的 PLM 充血反应的贡献尚未得到评估。通过动脉内药物输注，与单独抑制 NOS 相比，抑制一氧化氮合酶（NOS）、环氧化酶和细胞色素 P450（CYP450）途径的联合抑制并未进一步减弱对 PLM 的充血反应。
