Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla (Second try)

By: Sean D. Stocker, Susan M. Lang, Sarah S. Simmonds, Megan M. Wenner, William B. Farquhar (Hypertension, 2015)

Hypertension due to increased salt levels have been shown to be associated with increased levels of Na in cerebrospinal fluid (CSF) and increased sympathetic nerve activity (SNA). Those who are salt sensitive have seen an increased level of Na in the CSF. This study focuses more so on the effects of hypernatremia in CSF and how the pathway is relayed. The rostral ventrolateral medulla (RVLM) is involved in the signaling mechanism, but it is unclear how it is related to and increased concentration of Na. 

CSF with varying levels of Na concentrations were infused in male rats. During these infusions, recordings of the ABP and SNA were active. 

Various experiments were performed in order to test the different aspects of the study.

Experiment 1: Different concentrations of CSF NaCl were infused to observe effects on various end organs. Lumbar SNA, adrenal SNA, heart rate, and mean ABP were increased as concentration increased. Renal SNA decreased and splanchnic SNA was unchanged. 

Experiment 2: The Na levels was observed in the fourth ventricle of the brain. When CSF NaCl was infused, the concentration in the fourth ventricle was increased.

Experiment 3: To assess contribution of SNA to NaCl induced responses, infusions were performed after ganglionic blockade. Chlorisondamine was injected and decreased baseline SNA and mean ABP. It also abolished the SNA, tachycardiac, and pressor response to the NaCl injection. 

Experiment 5: To test whether RVLM neurons mediate a response to CSF NaCl, infusions occurred after the inhibition of the RVLM. Bilateral injections of GABA to RVLM reduced SNA activity in lumbar, renal, adrenal, splanchnic regions. Also, lumbar sympathoexcitatory and pressor response to the infusion was abolished. 

Experiment 6: To identify the neurotransmitter in the RVLM that mediates the responses in experiment 5, Na infusions were performed after blockade of ionotropic glutamate or angiotensin type 1 receptors in RVLM. Bilateral injection of kynurenic acid in RVLM partially reduced lumbar SNA but didn't change renal adrenal or splanchnic SNA, as well as mean ABP and heart rate. Blockade of glutamate receptors significantly weakened the increase in lumbar and adrenal SNA, as well as heart rate and ABP. It also reduced renal sympathoinhibitory response. Bilateral injection of angiotensin type 1 did not alter any of the responses. 

Experiment 7: Last experiment was to establish that CSF hypernatremia altered activity of barosensitive spinally projecting RVLM neurons. After infusion of NaCl in type 1 neurons occurred, cell discharge activity increased within 2 minutes and remained elevated. Decreased in Type 2 neurons. Type 3 neurons were unchanged. Identified C1 neurons displayed an increased discharge response to infusion of NaCl. 

The results led to the conclusions that acute infusions of different concentrations of NaCl increased lumbar SNA and adrenal SNA while decreasing renal SNA and not changing splanchnic SNA. In relation to the RVLM, sympathetic and ABP responses were reduced when the RVLM neurons were inhibited with a GABA agonist or glutamate receptor blockers. When the RVLM neurons were inhibited, the sympathetic and pressor responses to the NaCl was reduced, explaining the role of the RVLM in ABP and SNA control. We look at the splanchnic SNA and when RVLM neurons were inhibited, the response to increased NaCl was inhibited! The RVLM plays a role in how the SNA responses to increased levels of NaCl. 

-Tsetse Fly