Role for endothelin-1 in cardiometabolic dysfunction with intermittent hypoxia

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ID: 313969
2026
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Abstract
Endothelin-1 (ET-1) has been linked to increased hypoxic sensitivity of the chemoreceptors and the development of cardiometabolic disease. Repeated hypoxic exposures (i.e., intermittent hypoxia, IH) elicit increases in ET-1, muscle sympathetic nerve activity (MSNA), and blood pressure (BP). In this brief review, we summarize data from our group(s) which examined the effect of acute IH on MSNA, BP, and indices of adipose tissue lipolysis (i.e., free fatty acids, FFA) as well as the role of ET-1 in these responses. Herein we show acute ET receptor inhibition (oral bosentan) attenuates the rise in BP during hypoxia as well as the fall in BP during hyperoxia in healthy young men. Although the effect of IH on MSNA and BP was not attenuated following ET-receptor inhibition, IH increased plasma ET-1, epinephrine, and FFA concentrations. Notably, inhibition of ET-1 receptors with oral bosentan attenuated the IH-mediated rise in epinephrine and FFA. With these findings, we demonstrate a role for ET-1 in maintenance of resting BP in young men, possibly through a chemoreceptor-mediated mechanism. We further speculate the effect of ET-1 receptor inhibition on circulating FFA is secondary to its ability to reduce sympathoadrenal tone during IH exposure. Results highlighted in this review may serve as the basis for future work exploring ET-1 as a therapeutic target for cardiometabolic dysfunction associated with IH.
Reference Key
openalex_W7161545586 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Anna M. Gonsalves, SarahE. Baker, Prachi Singh, Jacqueline K. Limberg
Journal Food & function
Year 2026
DOI
10.1152/function.014.2026
URL
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