AUTHOR=Brown Courtney V. , Boulet Lindsey M. , Vermeulen Tyler D. , Sands Scott A. , Wilson Richard J. A. , Ayas Najib T. , Floras John S. , Foster Glen E. 

TITLE=Angiotensin II-Type I Receptor Antagonism Does Not Influence the Chemoreceptor Reflex or Hypoxia-Induced Central Sleep Apnea in Men

JOURNAL=Frontiers in Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00382

DOI=10.3389/fnins.2020.00382

ISSN=1662-453X

ABSTRACT=<p>Components of the renin-angiotensin system (RAS) situated within the carotid body or central nervous system may promote hypoxia-induced chemoreceptor reflex sensitization or central sleep apnea (CSA). We determined if losartan, an angiotensin-II type-I receptor (AT<sub>1</sub>R) antagonist, would attenuate chemoreceptor reflex sensitivity before or after 8 h of nocturnal hypoxia, and consequently CSA severity. In a double-blind, randomized, placebo-controlled, crossover protocol, 14 men (age: 25 ± 2 years; BMI: 24.6 ± 1.1 kg/m<sup>2</sup>; means ± SEM) ingested 3 doses of either losartan (50 mg) or placebo every 8 h. Chemoreceptor reflex sensitivity was assessed during hypoxic and hyperoxic hypercapnic ventilatory response (HCVR) tests and during six-20s hypoxic apneas before and after 8 h of sleep in normobaric hypoxia (F<sub><italic>I</italic></sub>O<sub>2</sub> = 0.135). Loop gain was assessed from a ventilatory control model fitted to the ventilatory pattern of CSA recorded during polysomnography. Prior to nocturnal hypoxia, losartan had no effect on either the hyperoxic (losartan: 3.6 ± 1.1, placebo: 4.0 ± 0.6 l/min/mmHg; <italic>P</italic> = 0.9) or hypoxic HCVR (losartan: 5.3 ± 1.4, placebo: 5.7 ± 0.68 l/min/mmHg; <italic>P</italic> = 1.0). Likewise, losartan did not influence either the hyperoxic (losartan: 4.2 ± 1.3, placebo: 3.8 ± 1.1 l/min/mmHg; <italic>P</italic> = 0.5) or hypoxic HCVR (losartan: 6.6 ± 1.8, placebo: 6.3 ± 1.5 l/min/mmHg; <italic>P</italic> = 0.9) after nocturnal hypoxia. Cardiorespiratory responses to apnea and participants’ apnea hypopnea indexes during placebo and losartan were similar (73 ± 15 vs. 75 ± 14 events/h; <italic>P</italic> = 0.9). Loop gain, which correlated with CSA severity (<italic>r</italic> = 0.94, <italic>P</italic> &lt; 0.001), was similar between treatments. In summary, in young healthy men, hypoxia-induced CSA severity is strongly associated with loop gain, but the AT<sub>1</sub>R does not modulate chemoreceptor reflex sensitivity before or after 8 h of nocturnal hypoxia.</p>