Mechanisms and neural circuits involved in the interaction between peripheral inflammation and sympathoexcitation in Renovascular Hypertension

• Grant number: 19/11196-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2019
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Eduardo Colombari
• Grantee: Pedro Lourenço Katayama
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 15/23467-7 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental hypertension and obesity, AP.TEM
• Associated scholarship(s): 21/13560-0 - Mechanisms of inflammation-induced sensitization of peripheral sensory systems, BE.EP.PD

Abstract

Recent evidence has demonstrated that Renovascular Hypertension is characterized not only by an increase in sympathetic activity and activation of the renin-angiotensin-aldosterone system, but also by a peripheral inflammation with increased levels of circulating pro-inflammatory cytokines. Although the conventional therapeutic approaches for hypertension have targeted a reduction of sympathetic activity and/or the renin-angiotensin-aldosterone system, little is known about controlling blood pressure by using anti-inflammatory approaches. Studies have suggested that circulating pro-inflammatory cytokines can act in central nervous system regions lacking blood brain barrier (circumventricular organs), activating central sympathetic pathways and increasing Arterial Blood Pressure (ABP). In addition, there is evidence suggesting that circulating pro-inflammatory cytokines could stimulate the carotid bodies, which are important players in cardiorespiratory regulation and known to be exaggeratedly activated in hypertension. The aim of the present study is to investigate the mechanisms and neural circuits involved in the interaction between peripheral inflammation and the autonomic nervous system in the pathophysiology of Renovascular Hypertension in rats. The hypothesis is that peripheral inflammation contributes to sympathetic activation and increase in ABP in this hypertension model. 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 ABP. To test this hypothesis, several approaches will be used including 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. It is expected that the results of the present study will provide better understanding of the mechanisms underlying the interaction between the immune system and the autonomic nervous system in the pathophysiology of Renovascular Hypertension, therefore contributing to identify new therapeutic targets for treating this disease. (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)

KATAYAMA, PEDRO L.; LEIRAO, ISABELA P.; KANASHIRO, ALEXANDRE; LUIZ, JOAO P. M.; CUNHA, FERNANDO Q.; NAVEGANTES, LUIZ C. C.; V. MENANI, JOSE; ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO. The carotid body detects circulating tumor necrosis factor-alpha to activate a sympathetic anti-inflammatory reflex. BRAIN BEHAVIOR AND IMMUNITY, v. 102, p. 17-pg., 2022-03-25. (19/11196-0, 15/23467-7)

KATAYAMA, PEDRO L.; LEIRAO, ISABELA P.; KANASHIRO, ALEXANDRE; MENANI, JOSE, V; ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO. The carotid body: A novel key player in neuroimmune interactions. FRONTIERS IN IMMUNOLOGY, v. 13, p. 10-pg., 2022-10-24. (19/11196-0, 19/24154-3, 15/23467-7)

KARLEN-AMARANTE, MARLUSA; ISABELA, I. P.; KATAYAMA, PEDRO L.; COLOMBARI, EDUARDO; BITTENCOURT-SILVA, PALOMA G.; MENEZES, MIGUEL F.; ZOCCAL, D. B.. Sympathetic dysregulation induced by postnatal intermittent hypoxia. Sleep, v. N/A, p. 13-pg., 2023-03-02. (13/17251-6, 20/05045-6, 19/11196-0)

KATAYAMA, PEDRO LOURENCO. Cardiorespiratory Dysfunction Induced by Brainstem Spreading Depolarization: A Potential Mechanism for SUDEP. JOURNAL OF NEUROSCIENCE, v. 40, n. 12, p. 3-pg., 2020-03-18. (19/11196-0)