Evaluation of renal sympathetic activity in DOCA-Sal hypertension: role of inflammation in peripheral and central responses

• Grant number: 23/17388-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ruy Ribeiro de Campos Junior
• Grantee: Edina da Luz Abreu
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/25295-0 - Communication between the central nervous system and kidneys: cardiovascular, renal and autonomic influences in physiological and physiopathological conditions, AP.TEM

Abstract

The increase in sympathetic vasomotor activity contributes to the cardiovascular and renal dysfunctions observed in arterial hypertension (AH). More recently, renal denervation has been used in hypertensive individual's refractory to pharmacological treatment. However, the mechanisms underlying renal sympathetic activation and its repercussions over time in AH are still poorly understood. In this project, we will use the DOCA-Salt model, which is characterized by increased renal sympathetic activity, hyperactivation of the brain renin-angiotensin system (RAS), and an inflammatory process in renal and brain tissue with a focus on investigating how the kidneys and the brain communicate. Initially, we will investigate the sympathetic actions mediated by the paraventricular nucleus of the hypothalamus (PVN) and the rostroventrolateral region of the medulla oblongata (RVLM) in DOCA-Sal rats with a focus on renal sodium transporters (NHE3 and ENaC). Furthermore, not only are renal sympathetic efferent actions involved in AH, but studies suggest that renal afferents contribute to sympathoexcitation in DOCA-Sal animals. Therefore, we will also evaluate the role of renal afferents in terms of neuroinflammation and renal inflammation in the model in question. Finally, recent evidence shows modifications in several central pathways, especially involving the RAS and expression of metalloproteases, such as ADAM-17, which are directly related to the activation of the central RAS, which participates in the activation and maintenance of sympathetic hyperactivity in DOCA-Salt animals. Finally, recent evidence shows modifications in several central pathways, especially involving the RAS and expression of metalloproteases, such as ADAM-17, which are directly related to the activation of the central RAS, which participates in the activation and maintenance of sympathetic hyperactivity in DOCA-Salt animals. Finally, recent evidence shows modifications in several central pathways, especially involving the RAS and expression of metalloproteases, such as ADAM-17, which are directly related to the activation of the central RAS, which participates in the activation and maintenance of sympathetic hyperactivity in DOCA-Salt rats. Therefore, this postdoctoral project aims to contribute to the scientific advancement of how the CNS and kidneys interrelate in a model of AH characterized by the hyperactivation of central pressor mechanisms that encompass two distinct central loops, that is, efferent and afferent signaling renal function and advance the understanding of the mechanisms of communication between kidneys and the CNS in arterial hypertension.