What is different in the RVLM of the SHR compared to normotensive rats?

Introduction: Previous evidence indicates that increased activity of RVLM neurons in SHR contributes to the increased blood pressure observed. This study amalgamates unpublished data aimed at identifying what is different in the SHR RVLM compared to the RVLM of normotensive animals.
Methods: Initially to test whether CaV3 channels contributed to hypertension the response to RVLM microinjection of nickel chloride (50mM) was compared in SHR, WKY and SD rats. The gene expression of CaV3.1,3.2,3.3 channels were then determined. As nickel can affect multiple systems in neurons a novel approach, label free shotgun proteomics, explored how the protein content in the RVLM differed in SHR and WKY. Results suggested mitochondria may be dysfunctional so, using serial block-face scanning electron microscopy of 75μm3 blocks of RVLM extracted from SHR and SD, mitochondria morphology was compared. In addition, microglia were studied using OX42 immunohistochemistry.
Results: Nickel chloride injections in SHR RVLM compared to SD and WKY RVLM had opposite cardiovascular and sympathetic effects however no differences were seen in the gene expression of Cav3.1,3.2 and 3.3 channels despite differences in RVLM abundance. As nickel can also directly increase oxidative stress, alter nNOS and potentiate NMDA channel activity the protein content of the RVLM was compared. There were 49 down regulated and 47 upregulated proteins in SHR compared to WKY. One major finding was that the lipid raft proteins, flotillin1 and 2, were significantly upregulated not only in the SHR RVLM but throughout the SHR brain potentially altering synaptic and extrasynaptic receptor clustering. Additional findings include evidence of increased glutamatergic and decreased GABA signalling, mitochondrial dysfunction including oxidative phosphorylation, increased microglial activity and reduced levels of transcription and translation in SHR. Although increased levels of OX42 were present in SHR RVLM no differences were found in the size or shape of microglia or mitochondria.
Conclusions: These results indicate that the SHR RVLM is different to that of normotensive animals and supports the idea of a hypoxia like environment where oxidative stress is elevated, excitatory signaling is increased, microglial activity is mildly increased and mitochondrial activity is compromised but not enough to alter mitochondrial dynamics. Flotillin 1/2 may be used as a marker of being SHR.