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Functional analysis of genes contributing to neurogenic hypertension

Grant number: 07/04085-0
Support type:Regular Research Grants
Duration: June 01, 2008 - May 31, 2011
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

High blood pressure (hypertension) affects up to a quarter of the adult population of Western countries. As it usually develops without causing any symptoms, the hypertension is known as "the silent killer". The central nervous system (CNS) plays an essential role on the pathogenesis of the hypertension and it is possible to assume that the causes of this pathology are strictly linked to changes in the expression of gene networks as well as in protein-protein interactions 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), nucleus of the solitary tract (NTS) and rostro-ventrolateral medulla (RVLM)Recent studies performed with gene microarrays techniques have shown a significant number of genes that are up or down-regulated within the PVN, NTS and RVLM of spontaneous hypertensive rats (SHR) when compared with the normotensive Wistar-Kyoto (WKY) as control. Among all genes differently expressed, we focus on the phosphoinositide 3-kinase (PI3K), which is up-regulated within the three central regions during the hypertensive stage. Moreover, the protein expressed by this gene is directly linked to the intracellular signalization of the angiotensin II (ANG II) pathways, which is considered one of the most important endogenous neuromodulator involved in the blood pressure control. Based on the results of gene microarrays and studies of the literature, our aim in the present project is to analyse the role of the PI3K as well as its interaction with the ANG II pathways in the PVN, NTS and RVLM on the pathogenesis of the hypertension in SHR compared to the WKY. For this we will be using the gene therapy with viral vectors transfer in vivo as well in the in situ with monitoring of blood pressure and sympathetic nerve activity, respectively. (AU)

Scientific publications (4)
(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, 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.
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. Web of Science Citations: 4.
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.
SABINO-SILVA, ROBINSON; CERONI, ALEXANDRE; KOGANEZAWA, TADACHIKA; MICHELINI, LISETE C.; MACHADO, UBIRATAN F.; ANTUNES, VAGNER R. Baroreceptor-mediated activation of sympathetic nerve activity to salivary glands. Physiology & Behavior, v. 107, n. 3, p. 390-396, OCT 10 2012. Web of Science Citations: 0.

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