Role of purinergic receptors of paraventricular nucleus of the hypothalamus in the neurogenic hypertension

• Grant number: 10/05037-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2010
• Effective date (End): September 30, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Vagner Roberto Antunes
• Grantee: Hildebrando Candido Ferreira Neto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 12/12444-8 - Evaluation of mechanisms of the sinaptic modulation and neuron-glia interaction of purinergic and glutamatergic receptors in the autonomic neurons of the paraventricular nucleus of the hypothalamus, BE.EP.DR

Abstract

Neurogenic hypertension (NH) is strictly linked to changes in the neurotransmission/neuromodulation within the specifics nuclei of the hypothalamic-brainstem circuitry that control the cardiovascular reflex and sympathetic activity. Among these nuclei are the paraventricular nucleus of the hypothalamus (PVN) that controls the autonomic and neuroendocrine function, with direct inputs to premotor sympathoexcitatory neurons in the rostroventrolateral medulla (RVLM) and/or to sympathetic preganglionic neurons of the intermediolateral cell column (IML) of the spinal cord. Several studies have shown that PVN is composed by a complex neuronal network of excitatory and inhibitory neurotransmitters with inputs to different areas of central nervous system involved in the control of the autonomic function and, consequently, the blood pressure level. Moreover, PVN neurons that project to RVLM have a significant expression of purinergic receptors that could be close correlated to the sympathetic overactivity observed in hypertension stage. Based on these findings our aim in the present project is to evaluate the role of purinergic receptors in NH at the PVN level by controlling of the sympathetic outflow in spontaneous hypertensive rats and normotensive rats. For this, we will be using nanoinjection of purinergic receptors agonists and/or antagonists in the PVN, simultaneously to sympathetic nerve recordings. Furthermore, we will be evaluating the co-transmission between purinergic and adrenergic pathways, as well as the interaction of neuron and glia of this nucleus on sympathetic outflow. Protein expression of P2X receptors (immunoblotting) and co-localization with adrenergic receptors (immunohistochemistry) of the PVN will be also investigated , for a better understanding of the mechanisms involved in NH.

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BUTTLER, L.; RIBEIRO, I. M.; FERREIRA-NETO, H. C.; ANTUNES, V. R.. Angiotensin II acting on PVN induces sympathoexcitation and pressor responses via the PI3K-dependent pathway. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 198, p. 54-58, JUL 2016. (09/01827-0, 10/05037-1, 10/17997-0, 13/06206-0)

RIBEIRO, NATALIA; PANIZZA, HELENA DO NASCIMENTO; DOS SANTOS, KAROLINE MARTINS; FERREIRA-NETO, HILDEBRANDO C.; ANTUNES, VAGNER ROBERTO. Salt-induced sympathoexcitation involves vasopressin V-1a receptor activation in the paraventricular nucleus of the hypothalamus. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 309, n. 11, p. R1369-R1379, DEC 1 2015. (13/06206-0, 10/05037-1, 10/17997-0, 09/13047-0)

FERREIRA-NETO, H. C.; YAO, S. T.; ANTUNES, V. R.. Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow. PURINERGIC SIGNALLING, v. 9, n. 3, p. 337-349, SEP 2013. (07/04085-0, 10/05037-1, 10/17997-0)

FERREIRA-NETO, H. C.; ANTUNES, V. R.; STERN, J. E.. Purinergic P2 and glutamate NMDA receptor coupling contributes to osmotically driven excitability in hypothalamic magnocellular neurosecretory neurons. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 14, p. 3531-3547, JUL 2021. (10/17997-0, 12/12444-8, 10/05037-1, 16/21991-3)

RIBEIRO, IZABELA MARTINA R.; FERREIRA-NETO, HILDEBRANDO C.; ANTUNES, VAGNER R.. Subdiaphragmatic vagus nerve activity and hepatic venous glucose are differentially regulated by the central actions of insulin in Wistar and SHR. PHYSIOLOGICAL REPORTS, v. 3, n. 5, MAY 2015. (07/04085-0, 09/13047-0, 10/05037-1, 13/06206-0)

FERREIRA-NETO, H. C.; RIBEIRO, I. M. R.; MOREIRA, T. S.; YAO, S. T.; ANTUNES, V. R.. PURINERGIC P2 RECEPTORS IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS ARE INVOLVED IN HYPEROSMOTIC-INDUCED SYMPATHOEXCITATION. Neuroscience, v. 349, p. 253-263, MAY 4 2017. (10/05037-1, 13/06206-0, 16/21991-3, 10/17997-0)

FERREIRA-NETO, HILDEBRANDO CANDIDO; ANTUNES, VAGNER R.; STERN, JAVIER E.. ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents. Journal of Neurophysiology, v. 114, n. 1, p. 159-169, JUL 1 2015. (07/04085-0, 10/05037-1, 12/12444-8, 10/17997-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERREIRA NETO, Hildebrando Candido. Study of the interaction between ATP and glutamate in neurons of the paraventricular nucleus of the hypothalamus and its relationship with the sympathoexcitatory response induced by changes in osmolarity.. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.