Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus

GABA(A) and GABA(B) receptors activation with agonists muscimol and baclofen, respectively in the lateral parabrachial nucleus (LPBN), induces water and hypertonic NaCl intake in rats. The purpose of this study was to examine the effects of previous injections of losartan (AT(1) angiotensin receptor...

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Authors: Silva, Camila Zambone Cardoso da [UNESP]; Menani, José Vanderlei [UNESP]; Callera, João Carlos [UNESP]
Format: Article
Status:Published version
Publication date:2011
Country:Brasil
Institution:UNESP
Repository:Repositório Institucional da UNESP
Language:English
OAI Identifier:oai:repositorio.unesp.br:11449/14998
Online Access:http://dx.doi.org/10.1016/j.brainresbull.2011.09.003
http://hdl.handle.net/11449/14998
Access Level:Open access
Keyword:GABA receptors
Angiotensin II
Losartan
Baclofen
Sodium appetite
Thirst
Lateral parabrachial nucleus
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author Silva, Camila Zambone Cardoso da [UNESP]
author2 Menani, José Vanderlei [UNESP]
Callera, João Carlos [UNESP]
author2_role author
author
author_browse Callera, João Carlos [UNESP]
Menani, José Vanderlei [UNESP]
Silva, Camila Zambone Cardoso da [UNESP]
author_facet Silva, Camila Zambone Cardoso da [UNESP]
Menani, José Vanderlei [UNESP]
Callera, João Carlos [UNESP]
author_role author
collection Repositório Institucional da UNESP
description GABA(A) and GABA(B) receptors activation with agonists muscimol and baclofen, respectively in the lateral parabrachial nucleus (LPBN), induces water and hypertonic NaCl intake in rats. The purpose of this study was to examine the effects of previous injections of losartan (AT(1) angiotensin receptor antagonist) into the LPBN on 0.3 M NaCl and water intake induced by baclofen injected bilaterally in the same area in fluid replete rats and in rats treated with the diuretic furosemide combined with a low dose of the angiotensin-converting enzyme inhibitor captopril injected subcutaneously. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Bilateral injections of baclofen (0.5 nmol/0.2 mu l, n=6) into the LPBN in fluid replete rats induced 0.3 M NaCl intake (22.4 +/- 6.5 vs. saline: 0.1 +/- 0.1 ml/210 min) and water intake (14.2 +/- 4.0 vs. saline: 0.6 +/- 0.6 ml/210 min) and pre-treatment of the LPBN with losartan (50 mu g/0.2 mu l,l) reduced 0.3 M NaCl intake (7.4 +/- 7.0 ml/210 min) and water intake (2.8 +/- 2.4 ml/210 min) induced by baclofen. In rats treated with furosemide + captopril, pre-treatment with losartan into the LPBN attenuated the increase in 0.3 M NaCl intake (13.3 +/- 3.2 vs. saline + baclofen: 24.3 +/- 3.9 ml/180 min) and water intake (4.8 +/- 2.1 vs. saline + baclofen: 19.5 +/- 6.6 ml/180 min) produced by baclofen. We conclude that baclofen may produce a non-specific blockade of the inhibitory mechanisms of LPBN (deactivation of LPBN inhibitory mechanisms) and this blockade is facilitated by angiotensin II acting on AT(1) receptors in the LPBN, which drives rats to ingest large amounts of water and hypertonic NaCl independent if rats are fluid depleted or normohydrated. (C) 2011 Elsevier B.V. All rights reserved.
eu_rights_str_mv openAccess
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institution UNESP
instname_str Universidade Estadual Paulista (UNESP)
language eng
network_acronym_str BR
network_name_str Brasil
oai_identifier_str oai:repositorio.unesp.br:11449/14998
publishDate 2011
publishDateSort 2011
publisher Pergamon-Elsevier B.V. Ltd
publisherStr Pergamon-Elsevier B.V. Ltd
reponame_str Repositório Institucional da UNESP
spelling Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus Silva, Camila Zambone Cardoso da [UNESP] Menani, José Vanderlei [UNESP] Callera, João Carlos [UNESP] GABA receptors Angiotensin II Losartan Baclofen Sodium appetite Thirst Lateral parabrachial nucleus GABA(A) and GABA(B) receptors activation with agonists muscimol and baclofen, respectively in the lateral parabrachial nucleus (LPBN), induces water and hypertonic NaCl intake in rats. The purpose of this study was to examine the effects of previous injections of losartan (AT(1) angiotensin receptor antagonist) into the LPBN on 0.3 M NaCl and water intake induced by baclofen injected bilaterally in the same area in fluid replete rats and in rats treated with the diuretic furosemide combined with a low dose of the angiotensin-converting enzyme inhibitor captopril injected subcutaneously. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Bilateral injections of baclofen (0.5 nmol/0.2 mu l, n=6) into the LPBN in fluid replete rats induced 0.3 M NaCl intake (22.4 +/- 6.5 vs. saline: 0.1 +/- 0.1 ml/210 min) and water intake (14.2 +/- 4.0 vs. saline: 0.6 +/- 0.6 ml/210 min) and pre-treatment of the LPBN with losartan (50 mu g/0.2 mu l,l) reduced 0.3 M NaCl intake (7.4 +/- 7.0 ml/210 min) and water intake (2.8 +/- 2.4 ml/210 min) induced by baclofen. In rats treated with furosemide + captopril, pre-treatment with losartan into the LPBN attenuated the increase in 0.3 M NaCl intake (13.3 +/- 3.2 vs. saline + baclofen: 24.3 +/- 3.9 ml/180 min) and water intake (4.8 +/- 2.1 vs. saline + baclofen: 19.5 +/- 6.6 ml/180 min) produced by baclofen. We conclude that baclofen may produce a non-specific blockade of the inhibitory mechanisms of LPBN (deactivation of LPBN inhibitory mechanisms) and this blockade is facilitated by angiotensin II acting on AT(1) receptors in the LPBN, which drives rats to ingest large amounts of water and hypertonic NaCl independent if rats are fluid depleted or normohydrated. (C) 2011 Elsevier B.V. All rights reserved. Brazilian public Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação para o Desenvolvimento da UNESP (FUNDUNESP) Univ Estadual Paulista, Sch Dent, Dept Basic Sci, BR-16018805 São Paulo, Brazil Univ Estadual Paulista, Sch Dent, Dept Physiol & Pathol, BR-16018805 São Paulo, Brazil FAPESP: 07/56280-0 Pergamon-Elsevier B.V. Ltd http://dx.doi.org/10.1016/j.brainresbull.2011.09.003 Brain Research Bulletin. Oxford: Pergamon-Elsevier B.V. Ltd, v. 86, n. 5-6, p. 348-354, 2011. 0361-9230 http://hdl.handle.net/11449/14998 10.1016/j.brainresbull.2011.09.003 WOS:000298711300008 WOS000298711300008.pdf 6656433539493879 8550526736462685
spellingShingle Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus
Silva, Camila Zambone Cardoso da [UNESP]
GABA receptors
Angiotensin II
Losartan
Baclofen
Sodium appetite
Thirst
Lateral parabrachial nucleus
status_str publishedVersion
title Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus
title_full Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus
title_fullStr Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus
title_full_unstemmed Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus
title_short Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus
title_sort Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus
topic GABA receptors
Angiotensin II
Losartan
Baclofen
Sodium appetite
Thirst
Lateral parabrachial nucleus
topic_facet GABA receptors
Angiotensin II
Losartan
Baclofen
Sodium appetite
Thirst
Lateral parabrachial nucleus
url http://dx.doi.org/10.1016/j.brainresbull.2011.09.003
http://hdl.handle.net/11449/14998