Astroglia Are a Possible Cellular Substrate of angiotensin(1-7) Effects in the Rostral Ventrolateral Medulla

Cardiovasc Res. 2010 Aug 1;87(3):578-84. doi: 10.1093/cvr/cvq059. Epub 2010 Mar 3.

Abstract

Aims: Angiotensin(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 results: Astrocytes, catecholaminergic (CA-ergic) and non-CA-ergic neurones were targeted with adenoviral vectors in organotypic slice cultures from Wistar rats and SHR. Astrocytic Ca(2+) signalling was monitored using a genetically engineered Ca(2+) sensor Case12. CA-ergic neurones expressed enhanced green fluorescent protein (EGFP) under control of the PRS x 8 promoter, whereas non-CA-neurones expressed EGFP under control of the synapsin-1 promoter. Neurones were recorded in whole cell mode while [Ca(2+)](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 AT(1) receptor blocker (losartan), suppressed Ang1-7-induced [Ca(2+)](i) elevations, which were also antagonized by blocking intracellular Ca(2+) stores. Ang1-7 evoked no consistent changes in [Ca(2+)](i) or membrane excitability in CA-ergic or non-CA-ergic neurones in either rat strain.

Conclusion: Astroglia 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I
  • Angiotensin II / analogs & derivatives
  • Angiotensin II / antagonists & inhibitors
  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Biosensing Techniques
  • Blood Pressure* / drug effects
  • Calcium Signaling
  • Catecholamines / metabolism
  • Disease Models, Animal
  • Genes, Reporter
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Losartan / pharmacology
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / metabolism*
  • Medulla Oblongata / physiopathology
  • Membrane Potentials
  • Microscopy, Confocal
  • Patch-Clamp Techniques
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Tissue Culture Techniques

Substances

  • 7-Ala-angiotensin (1-7)
  • Angiotensin II Type 1 Receptor Blockers
  • Catecholamines
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • angiotensin I (1-7)
  • Losartan