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Antioxidant mechanisms of sodium nitrite in a experimental hypertension model in rats

Grant number: 16/22846-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2017
Effective date (End): May 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:JOSE EDUARDO TANUS DOS SANTOS
Grantee:Jefferson Henrich Amaral
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Systemic arterial hypertension (SAH) is associated with a high mortality rate due to morphological and functional dysfunctions in the cardiovascular system. increased oxidative stress and reduced bioavailability of nitric oxide (NO) are closely implicated in these changes due to hypertension. Therefore, the search for therapeutic alternatives that decrease oxidative stress and increase the bioavailability of NO is increasing. Recently, studies have shown that NO oxidation metabolites, nitrate and nitrite, can be reduced to NO again and form nitrosothiols under certain conditions, conferring biological value to these considered inert ions previously.Following this line, our group and others have already demonstrated that sodium nitrite can exert antioxidant activity and decrease reactive oxygen species, especially during hypertension. However, it is still uncertain how nitrite can exert its antioxidant and antihypertensive effects. Nrf2 (Nuclear factor (erythroid-derived 2) -like 2) is considered a key regulator in the cellular antioxidant defenses system since genes activated by it ensure redox homeostasis of cells. In this context, studies demonstrate that NO donors and nitrosylated species can activate Nrf2 by mechanisms still to be explored. Therefore, the hypothesis of the present study is that treatment with oral sodium nitrite, when forming nitrosothioles, favors the activation of the Nrf2 pathway in resistance vessels of two kidneys,one-clip (2K1C) hypertensive animals, this promotes the transcription of antioxidant genes and thus antioxidant effect, resulting in the reduction of vasoconstriction and blood pressure, which would help to explain, at least in part, the antihypertensive effects of nitrite. (AU)