Exercise training increases GAD65 expression, restores the depressed GABA(A) receptor function within the PVN and reduces sympathetic modulation in hypertension

Autor(es)

Ferreira-Junior, Nilson C. ^[1] ; Ruggeri, Adriana ^[1] ; Silva Jr, Sebastiao D. ; Zampieri, Thais T. ^[2] ; Ceroni, Alexandre ^[2] ; Michelini, Lisete C. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

^[2] Silva Jr, Jr., Sebastiao D., Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHYSIOLOGICAL REPORTS; v. 7, n. 13 JUL 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 15/07863-0 - Melhora das alterações autonômicas com o exercício físico durante o processo de envelhecimento: exploração dos mecanismos moleculares e fisiológicos
• Beneficiário: Nilson Carlos Ferreira Junior
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/24935-4 - Barreira hematoencefálica e regulação autonômica na hipertensão arterial: efeitos da angiotensina ii e do treinamento aeróbio
• Beneficiário: Lisete Compagno Michelini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/10326-8 - Evolução temporal do controle autonômico e respostas cardiovasculares associadas em SHR jovens submetidos ao treinamento aeróbio
• Beneficiário: Adriana Ruggeri
• Modalidade de apoio: Bolsas no Brasil - Doutorado