N-ACETYL CYSTEINE: A MODULATOR OF THE ARTERIOBAROREFLEX IN OBSTRUCTIVE SLEEP APNEA.

Purpose: The CDC estimates that 18 million Americans have Obstructive Sleep Apnea (OSA). Although much is known clinically about OSA, the mechanisms which cause long term detrimental effects have not been fully elucidated. Prior research demonstrates that OSA causes a hypersympathetic state with decreased responsiveness to changes in blood pressure, i.e. decreased sensitivity of the arterial baroreflex (ABR). However, the mechanistic pathways underlying this decrease in ABR sensitivity remain to be identified. The goal of this study was to evaluate the potential role of reactive oxygen species (ROSs) in the modulation of the ABR in OSA. N-acetyl cysteine (NAC), a known free radical scavenger in the central nervous system (CNS), should diminish the depressive effects of intermittent hypoxia on ABR function. Thus, our hypothesis is that NAC will attenuate the sympathoexcitation observed after IH and, consequently, blunt the increase in HR typically observed. Methods: Positive and negative pressures were applied at the carotid sinus of 10 subjects using a malleable neck collar. Carotid baroreflex function (CBR) was assessed by comparing changes in heart rate for a given altered carotid sinus pressure. Blood pressure was non-invasively recorded using a finometer and heart rate was monitored by electrocardiography. After baseline measurements were recorded, the subjects were given a drink containing either NAC or a placebo treatment. After ingestion, the subjects were allowed to rest for 1 hour after which HR and CBR function were assessed. The subjects were then intermittent hypoxia trained (IHT) and HR and ABR function were obtained immediately, 30 min and 1 hour post IHT. Results: HR was found to increase with time under both placebo and NAC treatment conditions (two-way ANOVA, p ≥ 0.712). There were also no significant changes in CBR function as assessed by the operating or response ranges and maximum gain of the reflex. Conclusions: CBR control of HR, a measure of autonomic function, was not significantly altered in NAC treated subjects. This does not indicate an inability of NAC to modulate ABR function, but rather suggests other underlying mechanisms.