Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity

Abstract

Nearly two decades ago, we evaluated ten patients with obstructive sleep apnea (OSA). We determined that alarming nocturnal oscillations in arterial pressure and sympathetic nerve activity (SNA) were caused by regulatory coupling and neural interactions among SNA, apnea, and ventilation. Patients with OSA exhibited high levels of SNA when awake, during normal ventilation, and during normoxia, which contributed to hypertension and organ damage. Additionally, we achieved a beneficial and potentially lifesaving reduction in SNA through the application of continuous positive airway pressure (CPAP), which remains a primary therapeutic approach for patients with OSA. With these results in hindsight, we herein discuss three concepts with functional and therapeutic relevance to the integrative neurobiology of autonomic cardiovascular control and to the mechanisms involved in excessive sympathoexcitation in OSA.

Figure 1. Enhancement of SNA promotes cardiovascular disease.

(A) Under normal conditions, hypothalamic modulators, including aldosterone (Aldo), angiotensin ll (All), endothelin 1 (ET1), arginine vasopressin (AVP), NO, atrial natriuretic peptide (ANP), and cytokines, influence SNA. In healthy individuals, SNA is promoted by excitatory neural input (red) in response to peripheral stress. Simultaneously, peripheral responses (green), such as the arterial baroreceptor reflex and the cardiopulmonary and other vagal afferent reflexes, buffer the increase in SNA and maintain homeostasis. (B) Patients with OSA exhibit sustained excessive SNA, due to a pathological increase of excitatory neural input (red) and prevention and/or decrease of the protective inhibitory signals (green). Sustained SNA promotes proinflammatory immune responses and, ultimately, cardiovascular disease–associated end-organ damage.