Intermittent Hypoxia Enhances the Cardiogenic Sympathetic Afferent Reflex through Shared Activation of the cNTS-PVN-RVLM Network
Abstract
The Cardiogenic Sympathetic Afferent Reflex (CSAR) is a response triggered by the release of metabolites such as bradykinin during myocardial ischemia. Activation of the CSAR increases heart rate and arterial pressure to improve coronary perfusion; however, this elevates myocardial oxygen demand, potentially worsening ischemic injury. The magnitude of the CSAR is influenced by baseline sympathetic tone. Chronic elevations in sympathetic activity, such as those produced by intermittent hypoxia in obstructive sleep apnea (OSA), can heighten tone and augment the CSAR response. In the rat, acute intermittent hypoxia (AIH) models the sympathetic activation observed in OSA; however, the mechanism in which AIH enhances ischemic responses similar to CSAR remains unknown. Previous studies have identified an integrative network composed of the commissural nucleus tractus solitarii (cNTS), paraventricular hypothalamic nucleus of the hypothalamus (PVN), and rostral ventrolateral medulla (RVLM), which regulates sympathetic outflow by neural signaling to spinal sympathetic preganglionic neurons (SPNs). Modulation of this pathway, particularly the PVN–RVLM connection, is critical for generating a full CSAR response in hypertensive rats. Notably, AIH activates neurons within this same circuit, suggesting a shared neuronal population. We hypothesize that AIH-dependent augmentation of CSAR occurs through activation of a common neuronal population responsive to both intermittent hypoxia and the CSAR within the cNTS–PVN–RVLM network, leading to exacerbated sympathetic responses. To test this, we will use retrograde tracers to identify projection-defined neurons within the cNTS–PVN/RVLM network. We will then assess stimulus-induced neuronal activation following AIH or CSAR using c-Fos immune reactivity and determine the extent of overlap within these populations. These studies will define the central network responsible for AIH-dependent amplification of the CSAR and provide mechanistic insight into why patients with OSA are at increased risk for myocardial infarction and more severe ischemic injury.
Start Time
15-4-2026 9:00 AM
End Time
15-4-2026 12:00 PM
Room Number
Culp Ballroom 316
Poster Number
65
Presentation Type
Poster
Student Type
Graduate and Professional Degree Students, Residents, Fellows
Faculty Mentor
Matthew Zahner
Intermittent Hypoxia Enhances the Cardiogenic Sympathetic Afferent Reflex through Shared Activation of the cNTS-PVN-RVLM Network
Culp Ballroom 316
The Cardiogenic Sympathetic Afferent Reflex (CSAR) is a response triggered by the release of metabolites such as bradykinin during myocardial ischemia. Activation of the CSAR increases heart rate and arterial pressure to improve coronary perfusion; however, this elevates myocardial oxygen demand, potentially worsening ischemic injury. The magnitude of the CSAR is influenced by baseline sympathetic tone. Chronic elevations in sympathetic activity, such as those produced by intermittent hypoxia in obstructive sleep apnea (OSA), can heighten tone and augment the CSAR response. In the rat, acute intermittent hypoxia (AIH) models the sympathetic activation observed in OSA; however, the mechanism in which AIH enhances ischemic responses similar to CSAR remains unknown. Previous studies have identified an integrative network composed of the commissural nucleus tractus solitarii (cNTS), paraventricular hypothalamic nucleus of the hypothalamus (PVN), and rostral ventrolateral medulla (RVLM), which regulates sympathetic outflow by neural signaling to spinal sympathetic preganglionic neurons (SPNs). Modulation of this pathway, particularly the PVN–RVLM connection, is critical for generating a full CSAR response in hypertensive rats. Notably, AIH activates neurons within this same circuit, suggesting a shared neuronal population. We hypothesize that AIH-dependent augmentation of CSAR occurs through activation of a common neuronal population responsive to both intermittent hypoxia and the CSAR within the cNTS–PVN–RVLM network, leading to exacerbated sympathetic responses. To test this, we will use retrograde tracers to identify projection-defined neurons within the cNTS–PVN/RVLM network. We will then assess stimulus-induced neuronal activation following AIH or CSAR using c-Fos immune reactivity and determine the extent of overlap within these populations. These studies will define the central network responsible for AIH-dependent amplification of the CSAR and provide mechanistic insight into why patients with OSA are at increased risk for myocardial infarction and more severe ischemic injury.
