Cargando…

Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors

Objectives: Angiotensin II, glutamate and gamma-aminobutyric acid (GABA) interact within the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus (PVN) modulating the central regulation of blood pressure and sympathetic tone. Our aim was to assess the effects of local angiotensin II...

Descripción completa

Detalles Bibliográficos
Autores principales: Légat, Laura, Brouwers, Sofie, Smolders, Ilse J., Dupont, Alain G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474467/
https://www.ncbi.nlm.nih.gov/pubmed/28674483
http://dx.doi.org/10.3389/fnins.2017.00346
_version_ 1783244450152054784
author Légat, Laura
Brouwers, Sofie
Smolders, Ilse J.
Dupont, Alain G.
author_facet Légat, Laura
Brouwers, Sofie
Smolders, Ilse J.
Dupont, Alain G.
author_sort Légat, Laura
collection PubMed
description Objectives: Angiotensin II, glutamate and gamma-aminobutyric acid (GABA) interact within the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus (PVN) modulating the central regulation of blood pressure and sympathetic tone. Our aim was to assess the effects of local angiotensin II type 2 receptor stimulation within the RVLM and the PVN on neurotransmitter concentrations and mean arterial pressure (MAP). Methods: In vivo microdialysis was used for measurement of extracellular glutamate and GABA levels and for local infusion of the angiotensin II type 2 receptor agonist Compound 21 in the RVLM and the PVN of conscious normotensive Wistar rats. The MAP response to local Compound 21 was monitored with a pressure transducer under anaesthesia. Angiotensin II type 2 receptor selectivity was assessed using the angiotensin II type 2 receptor antagonist PD123319; the GABA-A receptor antagonist bicuculline was used to assess the involvement of GABA-A receptors. Results: Infusion of Compound 21 (0.05 μg/μl/h) in the RVLM significantly increased GABA levels and lowered blood pressure. These effects were abolished by co-infusion with PD123319. No changes in neurotransmitter levels or effects on blood pressure were seen with PD123319 infusion alone. Co-infusion of bicuculline abolished the Compound 21 evoked decrease in MAP. Infusion of Compound 21 within the PVN did not change extracellular neurotransmitter levels nor MAP. Conclusion: Selective stimulation of angiotensin II type 2 receptor within the RVLM by local Compound 21 infusion reduces blood pressure and increases local GABA levels in normotensive rats. This hypotensive response requires functional GABA-A receptors, suggesting that GABAergic neurons are involved in the sympatho-inhibitory action underlying this hypotensive response.
format Online
Article
Text
id pubmed-5474467
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-54744672017-07-03 Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors Légat, Laura Brouwers, Sofie Smolders, Ilse J. Dupont, Alain G. Front Neurosci Neuroscience Objectives: Angiotensin II, glutamate and gamma-aminobutyric acid (GABA) interact within the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus (PVN) modulating the central regulation of blood pressure and sympathetic tone. Our aim was to assess the effects of local angiotensin II type 2 receptor stimulation within the RVLM and the PVN on neurotransmitter concentrations and mean arterial pressure (MAP). Methods: In vivo microdialysis was used for measurement of extracellular glutamate and GABA levels and for local infusion of the angiotensin II type 2 receptor agonist Compound 21 in the RVLM and the PVN of conscious normotensive Wistar rats. The MAP response to local Compound 21 was monitored with a pressure transducer under anaesthesia. Angiotensin II type 2 receptor selectivity was assessed using the angiotensin II type 2 receptor antagonist PD123319; the GABA-A receptor antagonist bicuculline was used to assess the involvement of GABA-A receptors. Results: Infusion of Compound 21 (0.05 μg/μl/h) in the RVLM significantly increased GABA levels and lowered blood pressure. These effects were abolished by co-infusion with PD123319. No changes in neurotransmitter levels or effects on blood pressure were seen with PD123319 infusion alone. Co-infusion of bicuculline abolished the Compound 21 evoked decrease in MAP. Infusion of Compound 21 within the PVN did not change extracellular neurotransmitter levels nor MAP. Conclusion: Selective stimulation of angiotensin II type 2 receptor within the RVLM by local Compound 21 infusion reduces blood pressure and increases local GABA levels in normotensive rats. This hypotensive response requires functional GABA-A receptors, suggesting that GABAergic neurons are involved in the sympatho-inhibitory action underlying this hypotensive response. Frontiers Media S.A. 2017-06-19 /pmc/articles/PMC5474467/ /pubmed/28674483 http://dx.doi.org/10.3389/fnins.2017.00346 Text en Copyright © 2017 Légat, Brouwers, Smolders and Dupont. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Légat, Laura
Brouwers, Sofie
Smolders, Ilse J.
Dupont, Alain G.
Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors
title Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors
title_full Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors
title_fullStr Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors
title_full_unstemmed Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors
title_short Hypotensive Response to Angiotensin II Type 2 Receptor Stimulation in the Rostral Ventrolateral Medulla Requires Functional GABA-A Receptors
title_sort hypotensive response to angiotensin ii type 2 receptor stimulation in the rostral ventrolateral medulla requires functional gaba-a receptors
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474467/
https://www.ncbi.nlm.nih.gov/pubmed/28674483
http://dx.doi.org/10.3389/fnins.2017.00346
work_keys_str_mv AT legatlaura hypotensiveresponsetoangiotensiniitype2receptorstimulationintherostralventrolateralmedullarequiresfunctionalgabaareceptors
AT brouwerssofie hypotensiveresponsetoangiotensiniitype2receptorstimulationintherostralventrolateralmedullarequiresfunctionalgabaareceptors
AT smoldersilsej hypotensiveresponsetoangiotensiniitype2receptorstimulationintherostralventrolateralmedullarequiresfunctionalgabaareceptors
AT dupontalaing hypotensiveresponsetoangiotensiniitype2receptorstimulationintherostralventrolateralmedullarequiresfunctionalgabaareceptors