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Purinergic mechanisms at the hypothalamus level on sympathetic outflow and its correlation to neurogenic hypertension

Grant number: 10/17997-0
Support type:Regular Research Grants
Duration: March 01, 2011 - August 31, 2013
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Vagner Roberto Antunes
Grantee:Vagner Roberto Antunes
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Neurogenic hypertension (NH) is strictly linked to changes in the neurotransmission and/or neuromodulation within the specifics nuclei of the hypothalamic-brainstem circuitry that control the cardiovascular reflex and sympathetic outflow. Among these nuclei is 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. There are also evidences in the literature showing a synergism between purinergic and adrenergic neurotransmission, since an increase in the amplitude of miniature excitatory postsynaptic currents in response to norepinephrine in PVN neurons requires the release of ATP from glial cells and the increase in quantal efficacy results from an insertion of AMPA receptors, which contributes directly to the regulation of postsynaptic efficacy at glutamatergic synapses in the CNS. 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 regulating sympathetic outflow in spontaneous hypertensive and normotensive rats. For this, we will be injecting purinergic receptors agonists and/or antagonists in the PVN, simultaneously to the sympathetic nerve recordings. Furthermore, we will be evaluating the cotransmission 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. (AU)

Scientific publications (5)
(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)
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. Web of Science Citations: 1.
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. Web of Science Citations: 1.
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. Web of Science Citations: 10.
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. Web of Science Citations: 6.
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. Web of Science Citations: 6.

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