Impact of aging on conduit artery retrograde and oscillatory shear at rest and during exercise: role of nitric oxide.

Impact of aging on conduit artery retrograde and oscillatory shear at rest and during exercise: role of nitric oxide.
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DOI:
10.1161/hypertensionaha.110.165365
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发表时间:
2011-03
期刊:
Hypertension (Dallas, Tex. : 1979)
影响因子:
--
通讯作者:
Casey DP
Casey DP
中科院分区:
其他
文献类型:
--
作者:
Padilla J;Simmons GH;Fadel PJ;Laughlin MH;Joyner MJ;Casey DP

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最近,衰老与外周管道动脉中逆行和振荡剪切增加有关;血液动力学环境有利于促动脉粥样硬化内皮细胞表型。我们评估了阻力血管中一氧化氮(NO)的生物利用度是否有助于在静止时和有节奏的肌肉收缩期间上游导管动脉中剪切率模式的年龄相关差异。年轻(n=11,26±2岁)和老年(n=11,61±2岁)健康受试者接受动脉内生理盐水(对照)和NO合酶抑制剂NG-单甲基-L-精氨酸(L-NMMA)。肱动脉直径和速度通过多普勒超声测量在休息和在5分钟的回合有节奏的前臂运动。在休息时,老年受试者表现出肱动脉逆行和振荡切变(-13.2 ±3.0 s-1和0.11± 0.02 a.u.,分别)与年轻受试者(-4.8 ±2.3 s-1和0.04±0.02 a.u.,分别;均p<0.05)。年轻人前臂循环中的NO合酶抑制增加了逆行和振荡切变(均p<0.05),老年人和年轻人之间静息时的差异消失(均p>0.05)。从休息到稳态运动,老年受试者的逆行和振荡剪切力(均p<0.05)降低到组间无运动相关差异的程度(均p>0.05)。抑制前臂循环中的NO合酶并不影响两组运动中的逆行和振荡剪切(所有p>0.05)。这些数据首次表明,阻力血管中NO生物利用度的降低部分地导致了静息剪切模式中与年龄相关的差异,从而确定了导管动脉中动脉粥样硬化疾病风险增加的潜在机制。
Aging has been recently associated with increased retrograde and oscillatory shear in peripheral conduit arteries; a hemodynamic environment that favors a pro-atherogenic endothelial cell phenotype. We evaluated whether nitric oxide (NO) bioavailability in resistance vessels contributes to age-related differences in shear rate patterns in upstream conduit arteries at rest and during rhythmic muscle contraction. Young (n=11, 26±2 yr) and older (n=11, 61±2 yr) healthy subjects received intra-arterial saline (control) and the NO synthase inhibitor NG-Monomethyl-L-arginine (L-NMMA). Brachial artery diameter and velocities were measured via Doppler ultrasound at rest and during a 5-min bout of rhythmic forearm exercise. At rest, older subjects exhibited greater brachial artery retrograde and oscillatory shear (−13.2±3.0 s−1 and 0.11±.0.02 a.u., respectively) compared to young subjects (−4.8±2.3 s−1 and 0.04±0.02 a.u., respectively; both p<0.05). NO synthase inhibition in the forearm circulation of young, but not older, subjects increased retrograde and oscillatory shear (both p<0.05) such that differences between young and old at rest were abolished (both p>0.05). From rest to steady state exercise, older subjects decreased retrograde and oscillatory shear (both p<0.05) to the extent that no exercise-related differences were found between groups (both p>0.05). Inhibition of NO synthase in the forearm circulation did not affect retrograde and oscillatory shear during exercise in either group (all p>0.05). These data demonstrate for the first time that reduced NO bioavailability in the resistance vessels contributes, in part, to the age-related discrepancies in resting shear patterns, thus identifying a potential mechanism for increased risk of atherosclerotic disease in conduit arteries.