Astrocytes Contribute to Angiotensin II Stimulation of Hypothalamic Neuronal Activity and Sympathetic Outflow

Javier Eduardo Stern, Sookjin Son, Vinicia Campana Biancardi, Hong Zheng, Neeru Sharma, Kaushik P. Patel

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Angiotensin II (AngII) is a key neuropeptide that acting within the brain hypothalamic paraventricular nucleus regulates neurohumoral outflow to the circulation. Moreover, an exacerbated AngII action within the paraventricular nucleus contributes to neurohumoral activation in hypertension. Although AngII effects involve changes in paraventricular nucleus neuronal activity, the precise underlying mechanisms, cellular targets, and distribution of AngII receptors within the paraventricular nucleus remain largely unknown. Thus, whether AngII effects involve direct actions on paraventricular neurons, or whether it acts via intermediary cells, such as astrocytes, is still controversial. To address this important gap in our knowledge, we used a multidisciplinary approach combining patch-clamp electrophysiology in presympathetic paraventricular neurons and astrocytes, along with in vivo sympathetic nerve recordings and astrocyte-targeted gene manipulations. We present evidence for a novel mechanism underlying central AngII actions, which involves astrocytes as major intermediary cellular targets. We found that AngII type 1 receptor mRNA is expressed in paraventricular astrocytes. Moreover, we report that AngII inhibited glutamate transporter function, increasing in turn extracellular glutamate levels. This resulted in the activation of neuronal extrasynaptic NMDA (N-methyl-d-aspartate) receptors, increased presympathetic neuronal activity, enhanced sympathoexcitatory outflow, and increased blood pressure. Together, our studies support astrocytes as critical intermediary cell types mediating brain AngII regulation of the circulation and indicate that AngII-mediated neuronal and sympathoexcitatory effects are dependent on a unique neuroglial signaling modality involving nonsynaptic glutamate transmission.

Original languageEnglish (US)
Pages (from-to)1483-1493
Number of pages11
JournalHypertension
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Angiotensin II
Astrocytes
Paraventricular Hypothalamic Nucleus
Glutamic Acid
Amino Acid Transport System X-AG
Neurons
Angiotensin Type 1 Receptor
Angiotensin Receptors
Electrophysiology
Brain
Neuropeptides
Blood Pressure
Hypertension
Messenger RNA
Genes

Keywords

  • angiotensin
  • astrocyte
  • blood pressure
  • heart failure
  • hypothalamus

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Astrocytes Contribute to Angiotensin II Stimulation of Hypothalamic Neuronal Activity and Sympathetic Outflow. / Stern, Javier Eduardo; Son, Sookjin; Biancardi, Vinicia Campana; Zheng, Hong; Sharma, Neeru; Patel, Kaushik P.

In: Hypertension, Vol. 68, No. 6, 01.12.2016, p. 1483-1493.

Research output: Contribution to journalArticle

Stern, Javier Eduardo ; Son, Sookjin ; Biancardi, Vinicia Campana ; Zheng, Hong ; Sharma, Neeru ; Patel, Kaushik P. / Astrocytes Contribute to Angiotensin II Stimulation of Hypothalamic Neuronal Activity and Sympathetic Outflow. In: Hypertension. 2016 ; Vol. 68, No. 6. pp. 1483-1493.
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