Intra-arterial infusion of endothelin-1 significantly attenuated flow-mediated dilation from 2.4% to 0.5% and reactive hyperemia from 162 ml to 104 ml in young healthy subjects.
Does intra-arterial infusion of ET-1 impair reactive hyperemia and flow-mediated dilation in young healthy subjects?
Intra-arterial administration of ET-1 impairs both microvascular and conduit vessel function in young, healthy humans, highlighting the need for caution when using RH and FMD as markers in conditions with elevated ET-1.
Absolute Event Rate: 0.5% vs 2.4%
p-value: p=<0.05
Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml, and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) ( P < 0.05). Administration of ET-1 also reduced FMD (control: 2.4 ± 0.3%, ET-1: 0.5 ± 0.5%) and FMD normalized for shear rate (control: 10.5 × 10 −4 ± 2.0 × 10 −4% /s −1 , ET-1: 0.9 × 10 −4 ± 2.8 ×10 −4% /s −1 ). These findings reveal that elevated levels of ET-1 have a significant impact on vascular function, indicating that studies employing RH and FMD as markers of microvascular function and nitric oxide bioavailability, respectively, should exercise caution, as ET-1 can impact these assessments by tipping the balance between vasodilation and vasoconstriction, in favor of the latter. NEW & NOTEWORTHY Endothelin-1 (ET-1) is recognized as the body’s most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function.
Nishiyama et al. (Thu,) conducted a other in Healthy (n=7). Endothelin-1 (ET-1) intra-arterial infusion vs. Control (pre-infusion) was evaluated on Flow-mediated dilation (FMD) (p=<0.05). Intra-arterial infusion of endothelin-1 significantly attenuated flow-mediated dilation from 2.4% to 0.5% and reactive hyperemia from 162 ml to 104 ml in young healthy subjects.