Central chemoreceptors and sympathetic vasomotor outflow

Area of Science:

• Neuroscience
• Physiology
• Cardiovascular Regulation

Background:

• Sympathetic nerve discharge (SND) is crucial for maintaining cardiovascular homeostasis.
• Carbon dioxide (CO2) is a potent stimulus for respiratory and sympathetic regulation.
• The central nervous system mechanisms linking hypercapnia to sympathetic activation are not fully elucidated.

Purpose of the Study:

• To investigate the role of the rostral ventrolateral medulla (RVLM) in mediating sympathetic nerve discharge (SND) responses to hypercapnia.
• To identify the location of central chemoreceptors responsible for sensing CO2-induced sympathetic activation.
• To explore the interaction between respiratory and sympathetic neural networks in response to CO2.

Main Methods:

• Recording of SND, phrenic nerve discharge (PND), and RVLM neuronal activity in anesthetized, sino-aortic denervated, and vagotomized rats.
• Induction of hypercapnia by adjusting end-expiratory CO2 levels.
• Pharmacological manipulations using kynurenic acid (glutamate receptor antagonist) and muscimol (GABA receptor agonist) in specific brainstem nuclei (RVLM, RTN, rVRG/CVLM, commNTS).

Main Results:

• Hypercapnia significantly increased SND and RVLM neuronal activity.
• Injections into RVLM or RTN affected PND but not the CO2-induced SND increase.
• Injections into rVRG/CVLM eliminated PND and enhanced the CO2 effect on SND.
• Central chemoreceptors for CO2-induced SND are likely located in or near the RVLM, not NTS or rVRG/CVLM.
• Carotid body stimulation's effect on SND was blocked by interventions in RVLM or NTS.

Conclusions:

• CO2 increases SND primarily through the activation of RVLM sympathoexcitatory neurons.
• Central chemoreceptors sensing CO2 for sympathetic activation are proposed to be located within or close to the RVLM.
• RVLM neurons may be intrinsically pH-sensitive or receive input from RTN chemoreceptors.
• The central respiratory network modulates the sympathetic response to CO2, potentially via barosensitive neurons and RTN inhibition.