DOCA/salt hypertension alters Period1 and orexin-related gene expression in the medulla and hypothalamus of male rats: Diurnal influences

Dec 17, 2017Autonomic neuroscience : basic & clinical

High blood pressure from DOCA/salt changes daily patterns of clock and wakefulness-related genes in brain areas controlling body rhythms in male rats

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Abstract

Chronic aldosterone exposure increased saline intake at night and altered gene expression linked to the orexin system in the male Sprague Dawley rat brain.

DOCA/salt treatment elevated arterial pressure and lowered heart rate in the rats.
In the medulla oblongata, DOCA/salt upregulated the expression of the genes Per1, 11-HSD2, and α-ENAC regardless of the time of day.
A correlation was observed between the expression of orexin receptors (ORX-R1 and ORX-R2) and Per1 following DOCA/salt treatment, but not in control conditions.
In the hypothalamus, DOCA/salt treatment increased expression of Per1, orexin-A (ORX-A), and ORX-R2, with specific increases noted at night.
Gene expression changes in the orexin system may be influenced by aldosterone-induced alterations in Per1 expression.

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In peripheral tissues, aldosterone alters expression of multiple genes, including the clock gene Period 1 (Per1), 11 beta-hydroxysteroid dehydrogenase-2 (11-HSD2), and α-ENAC, the epithelial sodium channel subunit. We evaluated the impact of chronic aldosterone exposure (DOCA) and salt intake on nocturnal changes in gene expression in the male Sprague Dawley rat brain. Additionally, genes associated with the orexin (ORX) system were also evaluated based on the role of this neuropeptide in arousal, feeding and hypertension and an interconnection with Per1 expression. DOCA/salt treatment increased saline intake primarily at night, elevated arterial pressure and lowered heart rate. In the medulla oblongata, DOCA/salt upregulated Per1, 11-HSD2, and α-ENAC expression independent of time of day, but did not change ORX receptor type 1 (ORX-R1) or type 2 (ORX-R2) expression. ORX-R1, and ORX-R2 expression in the medulla did however correlate with Per1 expression following DOCA/salt treatment but not in controls. In the hypothalamus, DOCA/salt treatment upregulated Per1, ORX-A, and ORX-R2 expression, in general, and Per1 and ORX-A expression at night. ORX-A, ORX-R1 and ORX-R2 expression in the hypothalamus correlated with Per1 expression following DOCA/salt but not in controls. These findings demonstrate for the first time that DOCA/salt hypertension modulates ORX gene expression in the brain and suggest that changes in expression in the ORX system may occur directly or indirectly via aldosterone-induced changes in Per1 expression. Our findings also build on emerging evidence that monitoring gene expression during both the day and night is critical to understanding the role of specific genes in hypertension.

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DOCA/salt hypertension alters Period1 and orexin-related gene expression in the medulla and hypothalamus of male rats: Diurnal influences

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