Changes in GABAergic inputs in the paraventricular nucleus maintain sympathetic vasomotor tone in chronic heart failure

Changes in GABAergic inputs in the paraventricular nucleus maintain sympathetic vasomotor tone in chronic heart failure

Author Carillo, B. A. Autor UNIFESP Google Scholar
Oliveira-Sales, E. B. Autor UNIFESP Google Scholar
Andersen, M. Autor UNIFESP Google Scholar
Tufik, S. Autor UNIFESP Google Scholar
Hipolide, D. Autor UNIFESP Google Scholar
Santos, A. A. Autor UNIFESP Google Scholar
Tucci, P. J. Autor UNIFESP Google Scholar
Bergamaschi, C. T. Autor UNIFESP Google Scholar
Campos, R. R. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract The paraventricular nucleus (PVN) of the hypothalamus is an important region of the brain involved in the regulation of sympathetic vasomotor tone. Accumulating evidence supports the idea that a change in hypothalamic gamma-aminobutyric acid (GABA)-ergic inhibitory and glutamatergic excitatory inputs contribute to the exacerbated sympathetic drive in chronic heart failure (HF). the purpose of this study was to determine whether a possible imbalance between glutamatergic and GABAergic inputs to the PVN contributes to increased sympathetic outflow in HF in two different sympathetic territories. Renal (RSNA) and splanchnic sympathetic nerve activity (SSNA), mean arterial blood pressure (MAP) and heart rate were recorded from urethane-anesthetized HF or sham rats. the NMDA-glutamate and GABA-A receptor densities within the PVN were quantified in HF and sham rats by autoradiography. Bilateral microinjection of kynurenic acid (4 nmol) into the PVN decreased MAP and RSNA and SSNA in HF but not in sham rats. Furthermore, in response to GABA-A blockade in the PVN by bicuculline (400 pmol), hypertension and SSNA were reduced in HF compared to sham. the quantification of ionotropic NMDA receptors and GABA-A receptors in the PVN showed a significant reduction of GABA-A in HF rats; however, the NMDA density in the PVN did not differ between groups. Thus, this study provides evidence that the sympathoexcitation is maintained by an imbalance between GABAergic and glutamatergic inputs in the PVN in HF. the reduced GABAergic input results in relatively augmented glutamatergic actions in the PVN of HF rats. (C) 2012 Elsevier B.V. All rights reserved.
Keywords Heart failure
Autoradiograph
Glutamate
GABA
Renal
Splanchnic
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2012-11-02
Published in Autonomic Neuroscience-basic & Clinical. Amsterdam: Elsevier B.V., v. 171, n. 1-2, p. 41-48, 2012.
ISSN 1566-0702 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 41-48
Origin http://dx.doi.org/10.1016/j.autneu.2012.10.005
Access rights Closed access
Type Article
Web of Science ID WOS:000312417100008
URI http://repositorio.unifesp.br/handle/11600/35498

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