Effect of dietary salt intake on epithelial Na+ channels (ENaCs) in the hypothalamus of Dahl salt-sensitive rats.

Natalie J Mills,Katie Huang,Ryoichi Teruyama,Kaustubh Sharma

doi:10.14814/phy2.13838

Abstract

All three epithelial Na+ channel (ENaC) subunits (α, β, and γ) and the mineralocorticoid receptor (MR), a known regulator of ENaC, are located in vasopressin (VP) synthesizing magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. Our previous study showed that ENaC mediates a Na+ leak current that affects the steady‐state membrane potential of VP neurons. This study was conducted in Dahl salt‐sensitive (Dahl‐SS) rats to determine if any abnormal responses in the expression of ENaC subunits and MR occur in the hypothalamus and kidney in response to a high dietary salt intake. After 21 days of high salt consumption, Dahl‐SS rat resulted in a significant increase in γ ENaC expression and exhibited proteolytic cleavage of this subunit compared to Sprague–Dawley (SD) rats. Additionally, Dahl‐SS rats had dense somato‐dendritic γ ENaC immunoreactivity in VP neurons, which was absent in SD rats. In contrast, SD rats fed a high salt diet had significantly decreased α ENaC subunit expression in the kidney and MR expression in the hypothalamus. Plasma osmolality measured daily for 22 days demonstrated that Dahl‐SS rats fed a high salt diet had a steady increase in plasma osmolality, whereas SD rats had an initial increase that decreased to baseline levels. Findings from this study demonstrate that Dahl‐SS rats lack a compensatory mechanism to down regulate ENaC during high dietary salt consumption, which may contribute to the development of hypertension.

Highlights

In the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus, magnocellular neurosecretory cells (MNCs) synthesize the neurohypophysial hormones, vasopressin (VP) and oxytocin (OT)
The effect of dietary salt on the expression of epithelial Na+ channel (ENaC) subunits, VP, OT, and mineralocorticoid receptor (MR) in the hypothalamus of Dahl saltsensitive (Dahl-SS) rats was assessed by the relative difference in the amount of mRNA between groups for each of the genes (Fig. 1A)
This study demonstrated that the expression and abundance of ENaC within the hypothalamus of Dahl-SS rats is influenced by dietary salt

Summary

Introduction

In the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus, magnocellular neurosecretory cells (MNCs) synthesize the neurohypophysial hormones, vasopressin (VP) and oxytocin (OT). VP is released from the soma and dendrites of VP neurons located in the PVN to enhance the activity of the parvocellular neurons that project to the rostral ventrolateral medulla to cause an increase in sympathetic outflow and blood pressure (Son et al 2013). Given these systemic effects of VP, it is clear that VP plays an essential role in coordinating neuroendocrine and autonomic activities to maintain cardiovascular homeostasis. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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