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Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension
GABAergic inhibitory input within the paraventricular hypothalamic nucleus (PVN) plays a key role in restraining sympathetic outflow. Although experimental evidence has shown depressed GABA(A) receptor function plus sympathoexcitation in hypertension and augmented GABA levels with reduced sympatheti...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603325/ https://www.ncbi.nlm.nih.gov/pubmed/31264387 http://dx.doi.org/10.14814/phy2.14107 |
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author | Ferreira‐Junior, Nilson C. Ruggeri, Adriana Silva, Sebastião D. Zampieri, Thais T. Ceroni, Alexandre Michelini, Lisete C. |
author_facet | Ferreira‐Junior, Nilson C. Ruggeri, Adriana Silva, Sebastião D. Zampieri, Thais T. Ceroni, Alexandre Michelini, Lisete C. |
author_sort | Ferreira‐Junior, Nilson C. |
collection | PubMed |
description | GABAergic inhibitory input within the paraventricular hypothalamic nucleus (PVN) plays a key role in restraining sympathetic outflow. Although experimental evidence has shown depressed GABA(A) receptor function plus sympathoexcitation in hypertension and augmented GABA levels with reduced sympathetic activity after exercise training (T), the mechanisms underlying T‐induced effects remain unclear. Here we investigated in T and sedentary (S) SHR and WKY: (1) time‐course changes of hemodynamic parameters and PVN glutamic acid decarboxylase (GAD) isoforms’ expression; (2) arterial pressure (AP) and heart rate (HR) responses, sympathetic/parasympathetic modulation of heart and vessels and baroreflex sensitivity to GABA(A) receptor blockade within the PVN. SHR‐S versus WKY‐S exhibited higher AP and HR, increased sympathetic reduced parasympathetic modulation, smaller baroreflex sensitivity, and reduced PVN GAD65 immunoreactivity. SHR‐T and WKY‐T showed prompt maintained increase (2–8 weeks) in GAD65 expression (responsible for GABA vesicular pool synthesis), which occurred simultaneously with HR reduction in SHR‐T and preceded MAP fall in SHR‐T and resting bradycardia in WKY‐T. There was no change in GAD67 expression (mainly involved with GABA metabolic pool). Resting HR in both groups and basal MAP in SHR were negatively correlated with PVN GAD65 expression. Normalized baroreflex sensitivity and autonomic control observed only in SHR‐T were due to recovery of GABA(A) receptor function into the PVN since bicuculline administration abolished these effects. Data indicated that training augments in both groups the expression/activity of GABAergic neurotransmission within presympathetic PVN neurons and restores GABA(A) receptors′ function specifically in the SHR, therefore strengthening GABAergic modulation of sympathetic outflow in hypertension. |
format | Online Article Text |
id | pubmed-6603325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66033252019-07-12 Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension Ferreira‐Junior, Nilson C. Ruggeri, Adriana Silva, Sebastião D. Zampieri, Thais T. Ceroni, Alexandre Michelini, Lisete C. Physiol Rep Original Research GABAergic inhibitory input within the paraventricular hypothalamic nucleus (PVN) plays a key role in restraining sympathetic outflow. Although experimental evidence has shown depressed GABA(A) receptor function plus sympathoexcitation in hypertension and augmented GABA levels with reduced sympathetic activity after exercise training (T), the mechanisms underlying T‐induced effects remain unclear. Here we investigated in T and sedentary (S) SHR and WKY: (1) time‐course changes of hemodynamic parameters and PVN glutamic acid decarboxylase (GAD) isoforms’ expression; (2) arterial pressure (AP) and heart rate (HR) responses, sympathetic/parasympathetic modulation of heart and vessels and baroreflex sensitivity to GABA(A) receptor blockade within the PVN. SHR‐S versus WKY‐S exhibited higher AP and HR, increased sympathetic reduced parasympathetic modulation, smaller baroreflex sensitivity, and reduced PVN GAD65 immunoreactivity. SHR‐T and WKY‐T showed prompt maintained increase (2–8 weeks) in GAD65 expression (responsible for GABA vesicular pool synthesis), which occurred simultaneously with HR reduction in SHR‐T and preceded MAP fall in SHR‐T and resting bradycardia in WKY‐T. There was no change in GAD67 expression (mainly involved with GABA metabolic pool). Resting HR in both groups and basal MAP in SHR were negatively correlated with PVN GAD65 expression. Normalized baroreflex sensitivity and autonomic control observed only in SHR‐T were due to recovery of GABA(A) receptor function into the PVN since bicuculline administration abolished these effects. Data indicated that training augments in both groups the expression/activity of GABAergic neurotransmission within presympathetic PVN neurons and restores GABA(A) receptors′ function specifically in the SHR, therefore strengthening GABAergic modulation of sympathetic outflow in hypertension. John Wiley and Sons Inc. 2019-07-01 /pmc/articles/PMC6603325/ /pubmed/31264387 http://dx.doi.org/10.14814/phy2.14107 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Ferreira‐Junior, Nilson C. Ruggeri, Adriana Silva, Sebastião D. Zampieri, Thais T. Ceroni, Alexandre Michelini, Lisete C. Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension |
title | Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension |
title_full | Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension |
title_fullStr | Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension |
title_full_unstemmed | Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension |
title_short | Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension |
title_sort | exercise training increases gad65 expression, restores the depressed gaba(a) receptor function within the pvn and reduces sympathetic modulation in hypertension |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603325/ https://www.ncbi.nlm.nih.gov/pubmed/31264387 http://dx.doi.org/10.14814/phy2.14107 |
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