Endothelin-1 regulates arterial pulse wave velocity in vivo
Endothelin-1 regulates arterial pulse wave velocity in vivo
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DOI：
10.1016/j.jacc.2003.06.016
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发表时间：
2003-12-03
影响因子：
24
通讯作者：
Wilkinson, IB
中科院分区：
文献类型：
--
作者：
McEniery, CM;Qasem, A;Wilkinson, IB
目的通过测量活体脉搏波速度，研究局部作用的内皮素-1是否调节动脉扩张性。背景动脉僵硬是心血管风险的关键决定因素。一些证据支持内皮细胞通过释放血管活性介质来调节动脉僵硬的作用。然而，内皮素-1(ET-1)在调节动脉僵硬中的作用尚未被研究。结果动脉内注入ET-1可使髂总动脉脉搏波传导速度增加12+/-5%(P<0.001)，而注入内皮素-A受体拮抗剂BQ-123可使搏动波传导速度降低124%(p<；0.001)。输注BQ-123后，外源性ET-1对PWV无明显影响(-0.08+/-0.11%比-0.01+/-0.07%；p=0.53)。重要的是，在髂总动脉远端注入BQ-123或ET-1对PWV无影响。结论首次证实内源性ET-1在体内直接调节大动脉PWV。此外，外源性ET-1增加PWV，这可以被ETA受体阻断所钝化。这些观察部分解释了为什么ET-1上调的情况也与动脉硬化有关。因此，阻断ETA受体的药物可能有效地降低人类的大动脉僵硬，从而降低心血管风险。(C)2003年，由美国心脏病学会基金会提供。
OBJECTIVES The aim of this study was to investigate whether endothelin-1, acting locally, regulates arterial distensibility, assessed by measuring pulse-wave velocity in vivo.BACKGROUND Arterial stiffness is a key determinant of cardiovascular risk. Several lines of evidence support a role for the endothelium in regulating arterial stiffness by release of vasoactive mediators. However, the role of endothelin-1 (ET-1) in the regulation of arterial stiffness has not been investigated.METHODS All studies were conducted in anesthetized sheep. Pulse wave velocity (PWV) was calculated using the foot-to-foot methodology from two pressure waveforms simultaneously recorded with a high-fidelity, dual pressure-sensing catheter placed in the common iliac artery.RESULTS Intra-arterial infusion of ET-1 significantly increased iliac PWV by 12 +/- 5% (mean +/- STD; p < 0.001), whereas infusion of the endothelin-A (ETA) receptor antagonist BQ-123 significantly reduced PWV by 12 4% (p < 0.001). After BQ-123 infusion, exogenously infused ET-1 did not significantly change PWV compared with infusion of saline (change of -0.08 +/- 0.11% vs. -0.01 +/- 0.07%; p = 0.53). Importantly, infusion of BQ-123 or ET-1 distal to the common iliac artery did not affect PWV.CONCLUSIONS These results demonstrate, for the first time, that endogenous ET-1 production directly regulates large artery PWV in vivo. In addition, exogenous ET-1 increases PWV, and this can be blunted by ETA receptor blockade. These observations explain, in part, why conditions that exhibit up-regulation of ET-1 are also associated with arterial stiffening. Therefore, drugs that block ETA receptors may be effective in reducing large artery stiffness in humans, and thus cardiovascular risk. (C) 2003 by the American College of Cardiology Foundation.