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

Grant number: 19/11196-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2019
Effective date (End): July 31, 2022
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Eduardo Colombari
Grantee:Pedro Lourenço Katayama
Home 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

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)