Role for endothelin-1 in cardiometabolic dysfunction with intermittent hypoxia

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Metabolic Research

Background:

• Endothelin-1 (ET-1) is implicated in heightened chemoreceptor sensitivity to hypoxia and cardiometabolic disease development.
• Intermittent hypoxia (IH) exposure increases ET-1, muscle sympathetic nerve activity (MSNA), and blood pressure (BP).

Purpose of the Study:

• To investigate the role of ET-1 in the physiological responses to acute intermittent hypoxia (IH) in healthy young men.
• To examine the effects of ET-1 receptor inhibition on BP, MSNA, and lipolysis during IH.

Main Methods:

• Healthy young men underwent acute IH exposure.
• ET-1 receptor inhibition was achieved using oral bosentan.
• Measurements included BP, MSNA, plasma ET-1, epinephrine, and free fatty acids (FFA).

Main Results:

• Oral bosentan attenuated BP changes during hypoxia and hyperoxia.
• IH increased plasma ET-1, epinephrine, and FFA concentrations.
• Bosentan treatment attenuated IH-induced increases in epinephrine and FFA, but not MSNA or BP directly.

Conclusions:

• ET-1 plays a role in maintaining resting BP in young men, potentially via chemoreceptor pathways.
• ET-1 receptor inhibition may reduce sympathoadrenal tone during IH, impacting circulating FFA.
• ET-1 is a potential therapeutic target for cardiometabolic dysfunction linked to IH.