Trinity Joel D, Barrett-O'Keefe Zachary, Ives Stephen J, Morgan Garrett, Rossman Matthew J, Donato Anthony J, Runnels Sean, Morgan David E, Gmelch Benjamin S, Bledsoe Amber D, Richardson Russell S, Wray D Walter
aDepartment of Internal Medicine, University of UtahbGeriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical CentercUniversity of Utah Center on AgingdDepartment of Exercise and Sport ScienceeDepartment of Anesthesiology, University of Utah, Salt Lake City, Utah, USA.
J Hypertens. 2016 Feb;34(2):266-73. doi: 10.1097/HJH.0000000000000777.
Both altered shear rate and endothelin-1 (ET-1) are associated with the age-related development of atherosclerosis. However, the role of ET-1, a potent endogenous vasoconstrictor, in altering shear rate in humans, especially in the atherosclerotic-prone vasculature of the leg, is unknown. Therefore, this study examined the contribution of ET-1 to the age-related alterations in common femoral artery (CFA) shear rate.
BQ-123, a specific endothelin type A (ET(A)) receptor antagonist, was infused into the CFA, and diameter and blood velocity were measured by Doppler ultrasound in young (n = 8, 24 ± 2 years) and old (n = 9, 70 ± 2 years) study participants.
The old had greater intima-media thickening in the CFA, indicative of a preatherogenic phenotype. Prior to infusion, the old study participants exhibited reduced mean shear rate (27 ± 3/s) compared with the young study participants (62 ± 9/s). This difference was likely driven by attenuated antegrade shear rate in the old as retrograde shear rate was similar in the young and old. Inhibition of ETA receptors, by BQ-123, increased leg blood flow in the old, but not in the young, abolishing age-related differences. Older study participants had a larger CFA (young: 0.82 ± 0.03 cm, old: 0.99 ± 0.03 cm) in which BQ-123 induced significant vasodilation (5.1 ± 1.0%), but had no such effect in the young (-0.8 ± 0.8%). Interestingly, despite the age-specific, BQ-123-induced increase in leg blood flow and CFA diameter, shear rate patterns remained largely unchanged. Therefore, ET-1, acting through the ETA receptors, exerts a powerful age-specific vasoconstriction. However, removal of this vasoconstrictor stimulus does not augment mean shear rate in the old.
剪切速率改变和内皮素-1（ET-1）均与动脉粥样硬化的年龄相关发展有关。然而，ET-1这种强效内源性血管收缩剂在改变人体剪切速率中的作用，尤其是在腿部易发生动脉粥样硬化的血管中的作用尚不清楚。因此，本研究探讨了ET-1对股总动脉（CFA）剪切速率年龄相关改变的影响。
将特异性内皮素A（ET(A)）受体拮抗剂BQ-123注入CFA，并通过多普勒超声测量年轻（n = 8，24±2岁）和老年（n = 9，70±2岁）研究参与者的血管直径和血流速度。
老年人CFA的内膜中层增厚更明显，表明存在动脉粥样硬化前期表型。在注入前，老年研究参与者的平均剪切速率（27±3/s）低于年轻研究参与者（62±9/s）。这种差异可能是由于老年人顺行剪切速率减弱所致，因为年轻人和老年人的逆行剪切速率相似。BQ-123抑制ETA受体可增加老年人的腿部血流量，但对年轻人无此作用，消除了年龄相关差异。老年研究参与者的CFA较大（年轻：0.82±0.03 cm，老年：0.99±0.03 cm），其中BQ-123可诱导显著血管舒张（5.1±1.0%），但对年轻人无此作用（-0.8±0.8%）。有趣的是，尽管BQ-123诱导的腿部血流量和CFA直径增加具有年龄特异性，但剪切速率模式基本保持不变。因此，ET-1通过ETA受体发挥强大的年龄特异性血管收缩作用。然而，去除这种血管收缩刺激并不会增加老年人的平均剪切速率。
