PACAP-PAC1 Receptor Activation Is Necessary for the Sympathetic Response to Acute Intermittent Hypoxia

Area of Science:

• Neuroscience
• Cardiovascular Physiology
• Sleep Medicine

Background:

• Obstructive sleep apnea (OSA) involves repetitive hypoxia, leading to increased sympathetic activity and hypertension.
• Acute intermittent hypoxia (AIH) also induces persistent sympathetic nerve activity.
• The signaling pathways mediating these sympathetic responses are not fully understood.

Purpose of the Study:

• To investigate if the pituitary adenylate cyclase activating polypeptide (PACAP) signaling system mediates sympathetic nerve activity increases induced by AIH.
• To determine the role of the PAC1 receptor and cAMP in mediating the sympathetic response to AIH.

Main Methods:

• Utilized PACAP receptor knockout mice and Sprague Dawley rats.
• Administered pharmacological agents and measured blood pressure, heart rate, pH, PaCO2, and splanchnic sympathetic nerve activity under anesthesia.
• Investigated the effects of glutamate and PACAP microinjections/infusions into specific brain regions (RVLM) and the spinal cord.

Main Results:

• The sympathetic response to AIH is mediated via the PAC1 receptor in a cAMP-dependent manner.
• Intermittent PACAP signaling in the spinal cord drives persistent increases in sympathetic nerve activity during AIH.
• These sympathetic responses are independent of changes in blood pressure, pH, or PaCO2.

Conclusions:

• PACAP signaling in the spinal cord is crucial for generating sympathetic responses to AIH.
• This PACAP-mediated mechanism may represent a precursor to hypertension development in chronic intermittent hypoxia conditions like OSA.