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

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.

Astrocytes in neuroendocrine systems: An overview

“…AT 1 ‐R are expressed on both neurones and astrocytes, with both cell types displaying increases in Ca 2+ signalling in response to AngII treatment . In rats, AVP release and sodium intake in response to AngII treatment are blocked by the glial metabolic inhibitor fluorocitrate, indicating that glia may play a key role in AngII/AVP signalling . Decreased activity of hypothalamic GLT‐1, a glutamate transporter selectively expressed in astrocytes, following AngII treatment has been implicated in increasing activity of PVN neurones and enhancing sympathetic outflow .…”

“…134,135 In rats, AVP release and sodium intake in response to AngII treatment are blocked by the glial metabolic inhibitor fluorocitrate, indicating that glia may play a key role in AngII/AVP signalling. 136 Decreased activity of hypothalamic GLT-1, a glutamate transporter selectively expressed in astrocytes, following AngII treatment has been implicated in increasing activity of PVN neurones and enhancing sympathetic outflow. 137 Taken together, these data suggest action of AngII via astrocytes may help to re-establish fluid homeostasis after low blood pressure.…”

Vasopressin and Breathing: Review of Evidence for Respiratory Effects of the Antidiuretic Hormone

“…Angiotensin II is a potent hormone that causes vasoconstriction and activates the sympathetic nervous system, promotes renal reabsorption of sodium ions directly by acting on the renal tubules and indirectly through the aldosterone pathway ( Sztechman et al, 2018 ). It is also the key hormonal factor causing AVP release ( Fyhrquist et al, 1979 ; Flôr et al, 2018 ; Szczepanska-Sadowska et al, 2018 ). This allows for integration of water-electrolyte balance and regulation of osmolality and volume of extracellular fluid ( Szczepańska-Sadowska, 1996 ).…”