Alteration in flow (shear stress)-induced remodelling in rat resistance arteries with aging: improvement by a treatment with hydralazine
Alteration in flow (shear stress)-induced remodelling in rat resistance arteries with aging: improvement by a treatment with hydralazine
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DOI：
10.1093/cvr/cvm055
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发表时间：
2008-02-01
影响因子：
10.8
通讯作者：
Henrion, Daniel
中科院分区：
文献类型：
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作者：
Dumont, Odile;Pinaud, Frederic;Henrion, Daniel
衰老和血管疾病之间的联系仍然不清楚，特别是在阻力动脉中。由于内皮细胞的血管舒张能力下降通常在衰老中被描述，我们假设小动脉重塑对血流慢性增加的反应可能会改变。此外，我们测试了肼苯哒嗪的血管扩张剂治疗恢复重塑的能力，因为我们以前已经表明肼苯哒嗪对该过程具有强效作用。方法和结果（350 μ m直径），分别暴露于高血流量（HF）和正常血流量（NF），通过体内连续结扎二级动脉持续2周。在HF动脉，直径增加了21%，当管腔内压力为100毫米汞柱，在年轻大鼠超氧化物产生的上升。另一方面，在老年大鼠中，直径和超氧化物水平都没有增加。肼苯哒嗪恢复HF诱导的老年大鼠与超氧化物生成增加和超氧化物歧化酶（SOD）的表达减少的重塑。SOD模拟物4-羟基-2，2，6，6-四甲基哌啶氧基（TEMPOL）可阻止肼苯哒嗪对动脉直径的影响。在老年大鼠中，肼苯哒嗪增加了HF动脉中的动脉直径，而不增加eNOS表达。结论老年人阻力动脉血流重构不发生，但肼苯哒嗪通过活性氧依赖性机制恢复阻力动脉血流重构。在需要血流依赖性重塑的情况下，如缺血性和代谢性疾病，这些发现可能具有严重的病理生理学后果，在老年人中更常见。
Aims The link between aging and vascular diseases remains unclear, especially in resistance arteries. As a decreased vasodilator capacity of the endothelium is usually described in aging, we hypothesized that arteriolar remodelling in response to a chronic increase in blood flow might be altered. In addition, we tested the capacity of a vasodilator treatment with hydralazine to restore remodelling, as we have previously shown that hydralazine has a potent effect on the process.Methods and results Mesenteric resistance arteries (350 mu m diameter) from 3- and 24-month-old rats were exposed to high blood flow (HF) and normal blood flow (NF), for 2 weeks by sequential ligating second-order arteries in vivo. In HF arteries, diameter increased by 21% when intraluminal pressure was 100 mmHg, in association with a rise in superoxide production in young rats. On the other hand, both diameter and superoxide levels failed to increase in old rats. Hydralazine restored HF-induced remodelling in old rats in association with an increased superoxide production and a decreased superoxide dismutase (SOD) expression. The SOD-mimetic 4-hydroxy-2,2,6,6 -tetramethyl piperidinoxyl (TEMPOL) prevented the effect of hydralazine on the arterial diameter. In old rats, hydralazine increased the arterial diameter in HF arteries without increasing eNOS expression. Furthermore, hydralazine also restored HF remodelling in eNOS knockout mice.Conclusion Thus, flow remodelling in resistance arteries failed to occur in aging but it could be restored by hydralazine via a reactive oxygen species-dependent mechanism. These findings may have serious pathophysiological consequences in situations requiring flow-dependent remodelling such as ischaemic and metabolic diseases, more frequent in the elderly.