Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction

Area of Science:

• Cardiovascular Physiology
• Vascular Biology
• Human Physiology

Background:

• Endothelin-1 (ET-1) is a powerful vasoconstrictor involved in cardiovascular diseases.
• Its direct impact on human vascular function, particularly concerning microcirculation and conduit vessels, requires further elucidation.

Purpose of the Study:

• To investigate the acute effects of intra-arterial Endothelin-1 infusion on reactive hyperemia and flow-mediated dilation in the popliteal artery of healthy young adults.
• To assess the influence of ET-1 on basal leg blood flow and vascular responsiveness.

Main Methods:

• Seven healthy young subjects received intra-arterial infusions of ET-1.
• Reactive hyperemia (RH) and flow-mediated dilation (FMD) were measured in the popliteal artery after cuff occlusion.
• Basal leg blood flow, RH, and FMD were compared between control and ET-1 infusion conditions.

Main Results:

• ET-1 infusion significantly reduced basal leg blood flow, reactive hyperemia (AUC and peak values), and flow-mediated dilation.
• FMD normalized for shear rate was also significantly attenuated by ET-1.
• These results indicate a potent vasoconstrictive effect of ET-1 on both microvascular and conduit arteries.

Conclusions:

• Elevated Endothelin-1 levels significantly impair vascular function in healthy humans.
• The findings highlight that ET-1 can confound assessments of microvascular function (RH) and nitric oxide bioavailability (FMD).
• Caution is advised when interpreting RH and FMD in patient populations with increased ET-1 due to its potent vasoconstrictive properties.