Chronic ET(A) antagonist reverses hypertension and impairment of structure and function of peripheral small arteries in aortic stiffening.
Chronic ET(A) antagonist reverses hypertension and impairment of structure and function of peripheral small arteries in aortic stiffening.
复制标题
DOI：
10.1038/s41598-018-20439-5
复制
发表时间：
2018-02-15
影响因子：
4.6
通讯作者：
Kassab GS
中科院分区：
文献类型：
--
作者：
Guo X;Chen H;Han L;Haulon S;Kassab GS
动脉硬化可能是高血压的发病机制之一。本研究的目的是阐明内皮素-1（ET-1）通过激活ETA受体在主动脉硬化性高血压中的作用。通过在腹主动脉表面使用非收缩性约束装置NCR增加主动脉硬度。一组大鼠行主动脉NCR或假手术12周，然后用ETA受体拮抗剂BQ-123治疗3周。发现主动脉NCR 12周后，脉搏和平均压显著增加，外周血流模式改变，同时伴有血清ET-1水平升高（P <0.05）。主动脉僵硬度的增加（由脉搏波速度升高证明）导致肥厚性结构重塑和动脉顺应性降低，沿着外周小动脉内皮功能受损。BQ-123治疗仅部分减弱外周动脉肥大并恢复动脉顺应性，但完全恢复内皮功能，从而恢复局部血流并降低血压。我们的研究结果强调了主动脉硬化和外周动脉血管之间的血流动力学耦合和通过ETA依赖性机制的血流动力学。ETA受体阻滞剂可能在改善外周血管结构和功能方面具有治疗主动脉僵硬性高血压的潜力。
Arterial stiffness may contribute to the pathogenesis of hypertension. The goal of this study is to elucidate the role of Endothelin-1 (ET-1) in aortic stiffening-induced hypertension through ETA receptor activation. An increase in aortic stiffness was created by use of a non-constrictive restraint, NCR on the abdominal aortic surface. A group of rats underwent aortic NCR or sham operation for 12 weeks and were then treated with ETA receptor antagonist BQ-123 for 3 weeks. We found that 12 weeks of aortic NCR significantly increased pulse and mean pressure and altered peripheral flow pattern, accompanied by an increased serum ET-1 level (p < 0.05). The increase in aortic stiffness (evidenced by an elevated pulse wave velocity) caused hypertrophic structural remodeling and decreased arterial compliance, along with an impaired endothelial function in peripheral small arteries. BQ-123 treatment only partially attenuated peripheral arterial hypertrophy and restored arterial compliance, but completely recovered endothelium function, and consequently restored local flow and lowered blood pressure. Our findings underscore the hemodynamic coupling between aortic stiffening and peripheral arterial vessels and flow dynamics through an ETA-dependent mechanism. ETA receptor blockade may have therapeutic potential for improving peripheral vessel structure and function in the treatment of aortic stiffness-induced hypertension.
登录
查看更多内容
影响因子：
168.9
作者：
Anand, I;McMurray, J;Lüscher, TF
通讯作者：
Lüscher, TF
影响因子：
8.3
作者：
CHRISTENSEN, KL
通讯作者：
CHRISTENSEN, KL
影响因子：
9.8
作者：
HAAK, T;JUNGMANN, E;USADEL, KH
通讯作者：
USADEL, KH
影响因子：
8.3
作者：
Heerkens, EHJ;Shaw, L;Heagerty, AM
通讯作者：
Heagerty, AM
影响因子：
37.8
作者：
Amiri, F;Virdis, A;Schiffrin, EL
通讯作者：
Schiffrin, EL