Investigation into the mechanisms of neurogenic hypertension induced by peripheral and central inflammation

• Grant number: 22/00555-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2022
• End date: April 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: University of Tsukuba
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Eduardo Colombari
• Grantee: Eduardo Colombari
• Principal researcher abroad: Tadachika Koganezawa
• Institution abroad: University of Tsukuba, Japan
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Débora Simões de Almeida Colombari
• Associated research grant: 19/24154-3 - Development of new therapeutic strategies for treatment of cardiovascular diseases, AP.R

Abstract

In this research project, we hypothesized that peripheral and central inflammation contributes to sympathetic activation and increase in blood pressure. This effect would be mediated by circulating pro-inflammatory cytokines which activate receptors within the carotid bodies, the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ (SFO), stimulating central sympathetic pathways and resulting in increased blood pressure. To test this hypothesis, electrophysiological approaches, which will be mainly conducted in the application program, will give direct evidence that indicate cardiovascular sympathetic circuits in the central nervous system is hyperactivated by peripheral and central inflammation. Therefore, with the application research program, we try to have initial data and discuss details of further joint projects with extending into various approaches, such as telemetry, multiple sympathetic nerve recordings, optogenetics, microinjections of cytokine-receptors antagonists in central and peripheral areas involved in autonomic cardiovascular regulation, immunohistochemistry and in situ hybridization. And then, we will apply the JSPS-CAPES bilateral programs, the FAPESP grant and so on. References: FERNANDES, Marcos Vinicius; ROSSO MELO, Mariana; MOWRY, Francesca Elisabeth; LUCERA, Gabriela Maria; LAUAR, Mariana Ruiz; FRIGIERI, Gustavo; BIANCARDI, Vinicia Campana; MENANI, Jose V.; COLOMBARI, Débora Simões Almeida; COLOMBARI, Eduardo. Intracranial pressure during the development of renovascular hypertension. Hypertension, v. 77, p. 1311-1322, 2021 [doi: 10.1161/hypertensionaha.120.16217]; Pedro L. KATAYAMA, Isabela P. LEIRÃO, Alexandre KANASHIRO, João Paulo M. LUIZ, Fernando Q. CUNHA, Luiz C. C. NAVEGANTES, Jose V. MENANI, Daniel B. ZOCCAL, Débora S. A. COLOMBARI, Eduardo COLOMBARI. The carotid body detects circulating tumor necrosis factor-alpha to activate a sympathetic anti-inflammatory reflex. bioRxiv preprint [doi: 10.1101/2021.10.20.463417]. (AU)