Mechanisms involved in renal protein reabsorption in Renovascular Hypertension: a role for the renal nerve

• Grant number: 20/02617-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2020
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Erika Emy Nishi
• Grantee: Amanda Costa Veiga
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 22/08295-9 - The role of the renal sympathetic and sensory nervous systems on inflammation and oxidative damage in human proximal tubule cells during high albumin exposure, BE.EP.DR

Abstract

Studies have shown a strong neurogenic component in the onset of Arterial Hypertension (AH) in humans and experimental models. Renal denervation in hypertensive patients resistant to pharmacological treatment is an effective strategy in the control of Blood Pressure (BP), which has been attributed to the interruption of renal sympathetic and afferents fibers. Our previous studies showed a role for the renal nerves in maintaining AH and renal changes in experimental models of Renovascular Hypertension and Chronic Kidney Disease. In addition, reductions in fibrosis and oxidative stress markers and proteinuria were observed, associated with reduced activation of intrarenal Renin-Angiotensin System (RAS). High levels of proteinuria, mainly albuminuria, are considered a risk factor for cardiovascular diseases and changes in tubular mechanisms have been highlighted in the tubular interstitial lesion. Given the essential function of the renal nerve in renal function control, mainly the activation of RAS and tubular reabsorption of sodium, this project aims to evaluate whether the renal nerves are involved in the mechanisms of tubular reabsorption of proteins in renovascular hypertensive rats, treated or not with RAS blocker. In addition, it will be evaulated in vitro the possible effect of noradrenaline or Calcitonin Gene-Related Peptide (CGRP), associated or not with RAS blockade, in the tubular reabsorption of proteins and whether the megalin endocytic machinery is associated with changes in fibrogenic factors, oxidative stress and expression of RAS components in proximal tubule cells. (AU)

Scientific publications

(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)

MILANEZ, MAYCON I. O.; VEIGA, AMANDA C.; MARTINS, BEATRIZ S.; PONTES, ROBERTO B.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.; NISHI, ERIKA E.. Renal Sensory Activity Regulates the gamma-Aminobutyric Acidergic Inputs to the Paraventricular Nucleus of the Hypothalamus in Goldblatt Hypertension. FRONTIERS IN PHYSIOLOGY, v. 11, DEC 15 2020. (17/03905-5, 20/02617-9, 18/02671-3, 18/01898-4, 18/11909-3, 15/23809-5)

VEIGA, A. C.; SILVA-AGUIAR, R. P.; MILANEZ, M. I. O.; AIRES, R. S.; MORAES, Y. A. C.; CAMPOS, R. R.; BERGAMASCHI, C. T.; CARUSO-NEVES, C.; NISHI, E. E.. Renal nerves and hypertension contribute to impaired proximal tubule megalin-mediated albumin uptake in renovascular hypertensive rats. HYPERTENSION RESEARCH, v. N/A, p. 12-pg., 2025-01-17. (19/25295-0, 22/11063-2, 20/02617-9)