Sodium appetite elicited by low-sodium diet is dependent on p44/42 MAPK (ERK1/2) activation in the brain

Abstract

The sodium appetite is regulated by several signalling molecules, among which angiotensin II (ANG II) serves as a key driver of robust salt intake by binding to ANG II type 1 receptors (AT1R) in several regions in the brain. The activation of these receptors recruits the mitogen-activated protein kinase (MAPK) pathway, which has previously been linked to ANG II-induced increases in sodium appetite. Thus, we addressed the involvement of MAPK signalling in the induction of sodium appetite after four days of low-sodium diet consumption. An increase in extracellular signal-regulated kinase (ERK) phosphorylation in the laminae terminalis and mediobasal hypothalamus was observed after low-sodium diet consumption. This response was reduced by intracerebroventricular (icv) microinjection of an AT1R antagonist into the laminae terminalis but not the hypothalamus. This result indicates that low-sodium diet consumption activates the MAPK pathway via ANG II/AT1R signalling on the laminae terminalis. On the other hand, activation of the MAPK pathway in the mediobasal hypothalamus after low-sodium diet consumption seems to involve another extracellular mediator. We also evaluated whether a low-sodium diet could increase the sensitivity for ANG II in the brain and activate the MAPK pathway. However, icv injection of ANG II increased ERK phosphorylation on the laminae terminalis and mediobasal hypothalamus; this increase achieved a response magnitude similar to those in both the normal and low-sodium diet groups. These data indicate that low-sodium diet consumption for four days is insufficient to change the ERK phosphorylation response to ANG II in the brain. To investigate whether the MAPK pathway is involved in sodium appetite after low-sodium diet consumption, we performed icv microinjections of a MAPK pathway inhibitor (PD98059). PD98059 inhibited both saline and water intake after low-sodium diet consumption. Thus, the MAPK pathway is involved in the promoting the sodium appetite after low-sodium diet consumption.

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