Astroglia are a possible cellular substrate of angiotensin(1-7) effects in the rostral ventrolateral medulla

Fang Guo, Beihui Liu, Feige Tang, Samantha Lane, Ekaterina A. Souslova, Dmitriy M. Chudakov, Julian F.R. Paton, Sergey Kasparov

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

AimsAngiotensin(1-7) (Ang1-7) acting at the level of the rostral ventrolateral medulla (RVLM) affects arterial pressure. The cellular substrate of Ang1-7 remains unknown. We sought to determine which cell types in RVLM could mediate its actions and whether these are altered in the spontaneously hypertensive rat (SHR).Methods and resultsAstrocytes, catecholaminergic (CA-ergic) and non-CA-ergic neurones were targeted with adenoviral vectors in organotypic slice cultures from Wistar rats and SHR. Astrocytic Ca2+ signalling was monitored using a genetically engineered Ca2+ sensor Case12. CA-ergic neurones expressed enhanced green fluorescent protein (EGFP) under control of the PRS × 8 promoter, whereas non-CA-neurones expressed EGFP under control of the synapsin-1 promoter. Neurones were recorded in whole cell mode while [Ca2+]i was monitored using Rhod-2. RVLM astrocytes responded to Ang1-7 (200-1000 nM) with concentration-dependent [Ca 2+]i elevation. In SHR, the response to 1000 nM was significantly attenuated. The competitive Ang1-7 receptor antagonist A779, but not the AT1 receptor blocker (losartan), suppressed Ang1-7-induced [Ca2+]i elevations, which were also antagonized by blocking intracellular Ca 2+ stores. Ang1-7 evoked no consistent changes in [Ca2+]i or membrane excitability in CA-ergic or non-CA-ergic neurones in either rat strain.ConclusionAstroglia are a plausible cellular target of Ang1-7 in RVLM. Our data suggest that astrocytic responsiveness to Ang1-7 is reduced in SHR. We hypothesise that Ang1-7 modulates astrocytic signalling which in vivo may affect local metabolism and microcirculation, resulting in changes in activity of RVLM pre-sympathetic neurones and hence blood pressure.

Original languageEnglish
Pages (from-to)578-584
Number of pages7
JournalCardiovascular Research
Volume87
Issue number3
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

Keywords

  • Angiotensin(1-7)
  • Astroglia
  • Ca sensor Case12
  • Catecholaminergic neurones
  • Non-catecholaminergic neurones
  • Rostral ventrolateral medulla
  • Spontaneously hypertensive rat

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