Babcock Matthew C, DuBose Lyndsey E, Hildreth Kerry L, Stauffer Brian L, Kohrt Wendy M, Wenner Megan M, Moreau Kerrie L
Division of Geriatric Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
Division of Cardiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States.
Am J Physiol Regul Integr Comp Physiol. 2025 Mar 1;328(3):R253-R261. doi: 10.1152/ajpregu.00218.2024. Epub 2025 Jan 31.
Low testosterone in middle-aged/older men contributes to accelerated vascular aging, including endothelial dysfunction. However, the mechanisms by which low testosterone affects endothelial dysfunction are not well understood. We sought to determine whether higher endothelin-1 (ET-1) levels are associated with reduced brachial artery flow-mediated dilation (FMD) in middle-aged/older men with low testosterone. Plasma ET-1 was quantified in 60 men categorized as young ( = 20, age = 30 ± 4 yr, testosterone = 510 ± 63 ng/dL), middle-aged/older with normal testosterone ( = 20, age = 59 ± 6 yr, testosterone = 512 ± 115 ng/dL), or middle-aged/older with low testosterone ( = 20, age = 60 ± 8 yr, testosterone = 265 ± 47 ng/dL). Endothelial function was determined via brachial artery FMD. Venous and arterial endothelial cells were harvested via endovascular biopsy in a subset of participants and stained for ET-1 expression. Middle-aged/older men with normal testosterone exhibited lower brachial artery FMD (5.7 ± 2.2%) compared with young men (7.3 ± 1.3%, = 0.020), which was exaggerated in middle-aged/older men with low testosterone (4.0 ± 1.8%, = 0.010 vs. middle-aged/older men with normal testosterone). Plasma ET-1 was not different between young (5.6 ± 0.9 ng/dL) and middle-aged/older men with normal testosterone (6.0 ± 1.4 ng/dL, = 0.681) but was higher in middle-aged/older men with low testosterone (7.7 ± 2.8 ng/dL) compared with both groups ( < 0.001 vs. young men; = 0.013 vs. middle-aged/older men with normal testosterone). There was no difference in venous ( = 0.616) or arterial ( = 0.222) endothelial cell ET-1 expression between groups. There was a significant inverse association between plasma ET-1 and FMD ( =-0.371, = 0.004). These data suggest that the accelerated age-associated reduction in endothelial dysfunction in middle-aged/older men with low testosterone is related to higher circulating ET-1. Middle-aged/older men with low testosterone have reduced vascular endothelial function compared with young and age-matched men with normal testosterone. In this manuscript, we demonstrate that men with low testosterone have higher plasma endothelin-1, which is associated with worse brachial artery flow-mediated dilation. The source of higher plasma endothelin-1 remains unknown; however, higher circulating endothelin-1 appears to be a mechanism contributing to reduced vascular endothelial function in men with low testosterone.
中年/老年男性体内睾酮水平低会导致血管加速老化，包括内皮功能障碍。然而，低睾酮影响内皮功能障碍的机制尚不完全清楚。我们试图确定较高的内皮素-1（ET-1）水平是否与睾酮水平低的中年/老年男性肱动脉血流介导的血管舒张功能（FMD）降低有关。对60名男性进行血浆ET-1定量分析，这些男性分为年轻组（n = 20，年龄 = 30±4岁，睾酮 = 510±63 ng/dL）、睾酮水平正常的中年/老年组（n = 20，年龄 = 59±6岁，睾酮 = 512±115 ng/dL）或睾酮水平低的中年/老年组（n = 20，年龄 = 60±8岁，睾酮 = 265±47 ng/dL）。通过肱动脉FMD测定内皮功能。在一部分参与者中，通过血管内活检采集静脉和动脉内皮细胞，并对ET-1表达进行染色。睾酮水平正常的中年/老年男性肱动脉FMD（5.7±2.2%）低于年轻男性（7.3±1.3%，P = 0.020），而睾酮水平低的中年/老年男性这一指标更低（4.0±1.8%，与睾酮水平正常的中年/老年男性相比，P = 0.010）。年轻组（5.6±0.9 ng/dL）与睾酮水平正常的中年/老年组（6.0±1.4 ng/dL，P = 0.681）血浆ET-1无差异，但睾酮水平低的中年/老年男性血浆ET-1高于这两组（与年轻男性相比，P < 0.001；与睾酮水平正常的中年/老年男性相比，P = 0.013）。各组之间静脉（P = 0.616）或动脉（P = 0.222）内皮细胞ET-1表达无差异。血浆ET-1与FMD之间存在显著负相关（r = -0.371，P = 0.004）。这些数据表明，睾酮水平低的中年/老年男性与年龄相关的内皮功能障碍加速降低与循环中ET-1水平升高有关。与睾酮水平正常的年轻和年龄匹配男性相比，睾酮水平低的中年/老年男性血管内皮功能降低。在本研究中，我们证明睾酮水平低的男性血浆内皮素-1水平较高，这与肱动脉血流介导的血管舒张功能较差有关。血浆内皮素-1水平升高的来源尚不清楚；然而，循环中内皮素-1水平升高似乎是导致睾酮水平低的男性血管内皮功能降低的一种机制。
