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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: PHYSIOLOGICAL REPORTS; v. 7, n. 13 JUL 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 15/07863-0 - Amelioration of the autonomic imbalances of old age with exercise: exploring the molecular and physiological mechanisms
• Grantee: Nilson Carlos Ferreira Junior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/24935-4 - BLOOD-BRAIN BARRIER AND AUTONOMIC REGULATION IN HYPERTENSION: EFFECTS OF ANGIOTENSIN II AND AEROBIC TRAINING
• Grantee: Lisete Compagno Michelini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/10326-8 - Sequential changes of autonomic cardiovascular control in young SHR submitted to aerobic training
• Grantee: Adriana Ruggeri
• Support Opportunities: Scholarships in Brazil - Doctorate