Impact of DOCA‐Salt Hypertension on Gene Expression in the Dorsal Pons: a Microarray Analysis

Abstract

We had previously reported that induction of DOCA/salt hypertension altered the cardiovascular response to stress and this was associated with altered gene expression in the amygdala. Since a major source of afferent input to the amygdala originates from the dorsal pons, the present study was undertaken to evaluate how DOCA/salt hypertension alters gene expression in this brain region. Differential gene expression was measured by high‐density cDNA microarray analysis (Affymetrix Rat Gene Chip) and validated with real‐time PCR in DOCA‐salt hypertensive versus normotensive controls (n=4/group). Microanalysis identified 934 genes that were up‐regulated, including genes related to catecholamine synthesis and transport, inflammation, taste and smell. Solute carrier family 6 (dopamine neurotransmitter transporter) and tyrosine hydroxylase (TH) were the two most highly upregulated genes in DOCA/salt vs normotensive controls. Real‐time PCR analysis confirmed a 5.3 fold increase in dopamine transporter and a 10 fold increase in TH gene expression in the dorsal pons of the DOCA/salt treated animals vs controls. There was also evidence of up‐regulation of GFAP and IL‐10 and down regulation of glutamate receptors. Since changes in catecholamine release in both the amygdala and parabrachial nucleus can alter salt intake and catecholamine receptor activation in the lateral hypothalamus has been linked to salt intake gratification, our results raise the new possibility that alterations in catecholamine synthesis in the dorsal pons plays a significant role in DOCA driven salt intake.