Reflex Responses to Intermittent Hypoxia in Humans: Mechanisms and Consequences

Sleep apnea is the most common form of sleep disordered breathing and patients with sleep apnea exhibit persistent activation of the sympathetic nervous system. Sympathoexcitation is also the final common pathway for a host of complications in conditions like obesity, hypertension, sleep apnea, and heart failure and plays a significant role in predicting negative clinical outcomes and deteriorating cardiovascular health. However, the mechanisms of sympathoexcitation with sleep apnea are poorly understood and thus make effective therapeutic approaches difficult to develop.

Intermittent hypoxia (IH) has been implicated in animal models as the primary stimulus for evoking increases in sympathetic activity with recurrent apneas. Thus, the overall goal of this application is to better understand the effect of IH on sympathetic discharge patterns in humans as well as the mechanisms mediating persistent sympathoexcitation with IH. By better understanding the effect of IH on sympathoexcitation, targeted therapeutic approaches might be devised to mitigate the effects of sympathetic over-activity on the cardiovascular system in conditions such as sleep apnea.

Inclusion criteria

• healthy adult men and women;
• 18-45 years of age;
• BMI <30 kg/m2;
• non-pregnant/non-breastfeeding;
• non-smokers.

Exclusion criteria

Subjects will be excluded if they are:

• taking any medications known to affect the cardiovascular or autonomic nervous system (e.g. alpha-blockers, beta-blockers, etc);
• Apnea Hypopnea Index >10 events/hr

Self-reported history of:

• hepatic, renal, pulmonary, cardiovascular, or neurological disease;
• stroke or neurovascular disease;
• bleeding/clotting disorders;
• sleep apnea or other sleep disorders;
• diabetes;
• smoking;
• history of alcoholism or substance abuse;
• hypertension.