Systems biology of neuronal adaptation underlying central regulation of blood pressure

The objective of the present study is to characterize the gene regulation underlying hypertension‐induced central neuronal adaptation. We utilized a high‐throughput qPCR platform to obtain transcriptional profiles of select nuclei (NTS, CVLM, RVLM and CeA) in response to sustained hypertension induced by continuous intravenous infusion of phenylephrine up to 4h. We assayed 96 genes encoding proteins in the angiotensin II type 1 receptor (AT1R) pathway, key downstream transcription factors and ion channels. Our analysis revealed that sustained hypertension induces changes in several genes within 1h in NTS, and other nuclei showed a delayed response. We analyzed the data using a novel bioinformatics approach that identifies context‐specific signaling network that is consistent with our gene expression data. The networks with highly significant consistency showed remarkable similarity within the treatment groups but are distinct for hypertensive vs normotensive samples. Our analysis indicated that the AT1R pathway interactions are likely to be different across the brain regions, and conditionally dependent on the hypertensive state. Research Support: NIH ‐ R01 GM083108 , R33 HL088283 and R33 HL087361.