James R. Padley, Natasha N. Kumar, Qun Li, Thomas B.V. Nguyen, Paul M. Pilowslky, Ann K. Goodchild. Circulation Research (2007)
The rostral ventrolateral medulla (RVLM) is an area in the brainstem that regulates sympathetic nerve activity associated with blood pressure. The RVLM is known to have cholinergic inputs that affect its blood pressure regulation. The authors believe that nerves coming from the predunculopontine nucleus in the upper pons have cholinergic communication with the RVLM through the activation of muscarinic acetylcholine receptors (mAChR).
Seventeen male Sprague-Dawley rats were used in this study and placed under urethane anesthetics for the duration of the experiments. Two types of injections were used to alter the acetylcholine receptors. Oxotremorine sesquifumarate salt (OXO) is a mAChR agonist and scopolamine hydrobromide (SCOP) is a mAChR antagonist. When OXO was injected, mAChRs became activated and led to increases in blood pressure, splanchnic sympathetic nerve activity (SSNA), tail blood flow, and heart rate. OXO also caused phrenic nerve activity (PNA) to decrease, which reduces the respiratory rate. Sodium nitroprusside and phenylephrine injections were then given after OXO. Sodium nitroprusside is an inhibitory injection that causes vasodilation and phenylephrine is a G-protein receptor agonist which causes excitatory effects. The results showed that although these excited and inhibited states did still occur, they were at an overall higher blood pressure and SSNA compared to normal control rats. When SCOP was injected into the RVLM after OXO, blood pressure and SSNA returned to levels very similar to the control. OXO was then injected 30 minutes after SCOP and though it did show excitatory effects, it did not reach the initial OXO injection before SCOP.
Looking at the mechanisms in this pathway, the study shows that the cholinergic terminals synapse directly with sympathetic excitatory neurons in the RVLM. This was done by immunolabeling the vesicular acetylcholine transporters (vAChT), which showed a large buildup next to the RVLM neurons. When the RVLM sections were analyzed, all of the mAChR subtypes were shown to be expressed, but no spinally projecting tyrosine hydroxylase (TH) neurons expressed M2 receptors. TH is a marker for neurons that contain dopamine, norepinephrine, and epinephrine as neurotransmitters. Some non-TH spinally projecting neurons were shown to exhibit M2 receptors. Therefore if the OXO excitatory response is caused by M2 receptors in the TH neurons, then they must be located in a presynaptic location in the RVLM
The predunculopontine nucleus (PPT) is a group of neurons in the upper pons and was shown, in this study, to be a cholinergic pathway to the RVLM. The PPT cholinergic pathway was demonstrated by injecting cholera toxin B (CTB), which is used as a neuronal tracer, into the RVLM. The tracer CTB was then confirmed to be in a few areas, but only the PPT was shown to exhibit both CTB and VAChT. This suggests that the PPT is the only cholinergic input into the RVLM. The PPT was then stimulated using bicuculline and the results showed increased blood pressure and SSNA, which resembles the activation of mAChRs in the RVLM.
In conclusion, this study presents the cholinergic pathway from the PPT to the RVLM. In relation to our ongoing work in the lab, I think it would be interesting to see how other parts of the brainstem stimulate the RVLM itself, instead of outside injections. Although this study does present a cholinergic pathway from the PPT to the RVLM, they do not actually show the PPT stimulate the RVLM. It is suggested that when the PPT is stimulated, the RVLM is then stimulated, but I do not know if that can be assumed. If the PPT does in fact stimulate the RVLM, this could possibly be part of the descending efferent pathway responding to the baroreceptor afferents.
No comments:
Post a Comment