Endothelin-1 receptor blockade does not alter the sympathetic and hemodynamic response to acute intermittent hypoxia in men

• Published in: Journal of applied physiology (1985) 2022-10, Vol.133 (4), p.867-875
• Main Authors: Limberg, Jacqueline K, Baker, Sarah E, Ott, Elizabeth P, Jacob, Dain W, Scruggs, Zachariah M, Harper, Jennifer L, Manrique-Acevedo, Camila M
• Format: Article
• Language: English
• Subjects: Baroreflex - physiology; Blood Pressure - physiology; Bosentan; Endothelin-1; Endothelins; Heart Rate - physiology; Hemodynamics; Humans; Hypoxia; Male; Muscle, Skeletal; Oxygen; Receptor, Endothelin A; Sympathetic Nervous System - physiology
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00837.2021

Repeat exposures to low oxygen (intermittent hypoxia, IH), like that observed in sleep apnea, elicit increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in men. Endothelin (ET) receptor antagonists can attenuate the sympathetic and BP response to IH in rodents; whether these data translate to humans are unclear. We hypothesized that ET-receptor antagonism would ameliorate any rise in MSNA and BP following acute IH in humans. Twelve healthy men (31 ± 1 yr) completed two visits (control, bosentan) separated by at least 1 wk. MSNA, BP, and baroreflex sensitivity (modified Oxford) were assessed during normoxic rest before and following 30 min of IH. The midpoint (T50) for each individual's baroreflex curve was calculated. Acute IH increased plasma ET-1 ( < 0.01), MSNA burst frequency ( = 0.03), and mean BP ( < 0.01). There was no effect of IH on baroreflex sensitivity ( = 0.46), although an increase in T50 was observed ( < 0.01). MSNA burst frequency was higher ( = 0.04) and mean BP ( < 0.01) was lower following bosentan treatment compared with control. There was no effect of bosentan on baroreflex sensitivity ( = 0.53), although a lower T50 was observed on the bosentan visit ( < 0.01). There was no effect of bosentan on increases in MSNA ( = 0.81) or mean BP ( = 0.12) following acute IH. Acute IH results in an increase in ET-1, MSNA, and BP in healthy young men. The effect of IH on MSNA and BP is not attenuated following ET-receptor inhibition. Present data suggest that acute IH does not increase MSNA or BP through activation of ET-receptors in healthy young men. Repeat exposures to low oxygen (intermittent hypoxia, IH) elicit increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in men. Endothelin (ET) receptor antagonists can attenuate the sympathetic and BP response to IH in rodents; whether these data translate to humans were unclear. We show acute IH results in an increase in ET-1, MSNA, and BP in healthy young men; however, the effect of IH on MSNA and BP does not occur through activation of ET-receptors in healthy young men.