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Title of article :
Endothelin-1 regulates arterial pulse wave velocity in vivo
Author/Authors :
Carmel M. McEniery، نويسنده , , Ahmad Qasem، نويسنده , , Matthias Schmitt، نويسنده , , Albert P Avolio، نويسنده , , John R Cockcroft، نويسنده , , Ian B Wilkinson، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2003
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Abstract :
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.
Keywords :
heart rate , LNMMA , MAP , NG-monomethyl-L-arginine , mean arterial pressure , NA , noradrenaline , NO , PWV , ET-1 , ETA , TT , Pulse wave velocity , Endothelin-A , transit time , HR , endothelin-1 , nitric oxide
Journal title :
JACC (Journal of the American College of Cardiology)
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