Glial Cells Are Involved in ANG-II-Induced Vasopressin Release and Sodium Intake in Awake Rats.

Atalia F L Flôr,José L De Brito Alves,Lucila L K Elias,Valdir A Braga,Maria S França-Silva,Camille M Balarini,Josiane C Cruz,José Antunes-Rodrigues,Silvia G Ruginsk

doi:10.3389/fphys.2018.00430

Abstract

It is known that circulating angiotensin II (ANG-II) acts on the circumventricular organs (CVOs), which partially lack a normal blood-brain barrier, to stimulate pressor responses, vasopressin (AVP), and oxytocin (OT) secretion, as well as sodium and water intake. Although ANG-II type 1 receptors (AT1R) are expressed in neurons and astrocytes, the involvement of CVOs glial cells in the neuroendocrine, cardiovascular and behavioral responses induced by central ANG II remains to be further elucidated. To address this question, we performed a set of experiments combining in vitro studies in primary hypothalamic astrocyte cells (HACc) and in vivo intracerebroventricular (icv) microinjections into the lateral ventricle of awake rats. Our results showed that ANG-II decreased glutamate uptake in HACc. In addition, in vivo studies showed that fluorocitrate (FCt), a reversible glial inhibitor, increased OT secretion and mean arterial pressure (MAP) and decreased breathing at rest. Furthermore, previous FCt decreased AVP secretion and sodium intake induced by central ANG-II. Together, our findings support that CVOs glial cells are important in mediating neuroendocrine and cardiorespiratory functions, as well as central ANG-II-induced AVP release and salt-intake behavior in awake rats. In the light of our in vitro studies, we propose that these mechanisms are, at least in part, by ANG-II-induced astrocyte mediate reduction in glutamate extracellular clearance.

Highlights

Hypovolemia produced by dehydration, salt loading or water deprivation induces a marked increase in circulating Angiotensin II (ANG-II), which modulates body fluid and cardiorespiratory homeostasis through circumventricular organs (CVOs)
Our data showed that central acute inhibition of glial cells decreased AVP secretion and salt intake induced by central ANG-II
Our results suggest that CVOs glial cells are important in integrating signaling which acts to modulate body fluid and Control 5′ 10′ 15′ 30′

Summary

Introduction

Hypovolemia produced by dehydration, salt loading or water deprivation induces a marked increase in circulating ANG-II, which modulates body fluid and cardiorespiratory homeostasis through circumventricular organs (CVOs). In vitro studies have shown that ANG-II in isolated SFO, OVLT neurons or astrocytes induce calcium transients waves (Li and Ferguson, 1993; Gebke et al, 1998), suggesting that these cells could be important intermediates involved in the hydromineral and cardiorespiratory homeostasis induced by central ANG-II. Hypothalamic astrocytes appear to be functionally critical for ANG II-induced fluid balance and hemodynamic homeostasis, since an elegant study by Stern et al (2016), combining in vitro patch-clamp and in vivo approaches showed that ANG-II in the PVN inhibited astrocyte-specific glutamate transporter (GLT-1) activity, inducing increased extracellular glutamate levels, which contributed to increased pre-sympathetic neuronal activity, sympathoexcitatory outflow, and blood pressure.

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