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Involvement of oxidative stress and pro-inflammatory cytokines in hypertension

Grant number: 13/05189-4
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2013
Effective date (End): February 28, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:José Vanderlei Menani
Grantee:Mariana Ruiz Lauar
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:11/50770-1 - Neural mechanisms involved of hydroelectrolytic balance and cardiorespiratory control, AP.TEM

Abstract

The results obtained during the scientific initiation of the candidate demonstrated that intracerebroventricular (ICV) injections of hydrogen peroxide (H2O2) or the catalase inhibitor 3-amino-1 ,2,4-triazole (ATZ) acutely reduce the pressor response induced by ICV angiotensin II (ANG II) in normotensive rats, spontaneously hypertensive rats(SHR) or renovascular hypertensive rats (2 kidneys, 1 clip - 2K1C). Intravenous (IV) injections of ATZ in normotensive rats or 2K1C hypertensive rats also reduced the pressor response produced by ICV injection of ANG II. The combination of H2O2 ICV with ATZ IV or ICV abolished the pressor response of ICV ANG II in normotensive rats and also reduced the baseline arterial pressure of SHR and 2K1C hypertensive rats. Given that the increase in H2O2 acute availability in SHR or 2K1C hypertensive rats led to a smaller ANG II-induced pressor response and a decrease in baseline arterial pressure, one of the objectives of the present project is to test whether the effect of chronic (4 weeks) subcutaneous (SC) or ICV administration of ATZ on baseline blood pressure in normotensive rats, SHR and 2K1C hypertensive rats using tail-cuff plethysmography or telemetry methods. Recent studies have also suggested that activation of central mechanisms during hypertension is associated with a state of inflammation, causing microglia activation, increase in pro-inflammatory cytokines (IL-1, IL-6, TNF-±) and decrease in anti-inflammatory cytokines (IL-10). The superoxide dismutase mimetic tempol, which reduces the availability of superoxide anion, was able to reduce blood pressure and renal sympathetic activity in 2K1C hypertensive rats. Thus, another objective of this project is to investigate whether the chronic SC or ICV treatment with ATZ or tempol affect the levels of inflammatory cytokines and microglia activation in the paraventricular nucleus of the hypothalamus (PVN) and in the rostral ventrolateral medulla (RVLM). It will also be investigated if SC or ICV ATZ or tempol would affect c-Fos protein expression in vasopressinergic neurons of the PVN, the barorefex test, sympathetic activity, daily water and food intake, body weight, and renal excretion and the correlation of these changes with any changes in blood pressure in SHR or 2K1C hypertensive rats. Additionally we will also investigate the effects of bilateral injections of H2O2 or ATZ into the PVN and RVLM on blood pressure of hypertensive rats as well as on pressor responses induced by ANG II and glutamate injected on these areas. (AU)

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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)
LAUAR, MARIANA R.; BLANCH, GRAZIELA T.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; DE PAULA, PATRICIA M.; DE LUCA JR, LAURIVAL A.; MENANI, V, JOSE. Anti-hypertensive effect of hydrogen peroxide acting centrally. HYPERTENSION RESEARCH, MAY 2020. Web of Science Citations: 0.
DAVID, RICHARD B.; RONCARI, CAMILA F.; LAUAR, MARIANA R.; VENDRAMINI, REGINA C.; ANTUNES-RODRIGUES, JOSE; MENANI, JOSE V.; DE LUCA, JR., LAURIVAL A. Sodium intake, brain c-Fos protein and gastric emptying in cell-dehydrated rats treated with methysergide into the lateral parabrachial nucleus. Physiology & Behavior, v. 151, p. 111-120, NOV 1 2015. Web of Science Citations: 1.

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