title: Consistent antioxidant and antihypertensive effects of oral sodium nitrite in DOCA-salt hypertension.
abstract: Hypertension is a common disease that includes oxidative stress as a major feature, and oxidative stress impairs physiological nitric oxide (NO) activity promoting cardiovascular pathophysiological mechanisms. While inorganic nitrite and nitrate are now recognized as relevant sources of NO after their bioactivation by enzymatic and non-enzymatic pathways, thus lowering blood pressure, mounting evidence suggests that sodium nitrite also exerts antioxidant effects. Here we show for the first time that sodium nitrite exerts consistent systemic and vascular antioxidant and antihypertensive effects in the deoxycorticosterone-salt (DOCA-salt) hypertension model. This is particularly important because increased oxidative stress plays a major role in the DOCA-salt hypertension model, which is less dependent on activation of the renin-angiotensin system than other hypertension models. Indeed, antihypertensive effects of oral nitrite were associated with increased plasma nitrite and nitrate concentrations, and completely blunted hypertension-induced increases in plasma 8-isoprostane and lipid peroxide levels, in vascular reactive oxygen species, in vascular NADPH oxidase activity, and in vascular xanthine oxidoreductase activity. Together, these findings provide evidence that the oral administration of sodium nitrite consistently decreases the blood pressure in association with major antioxidant effects in experimental hypertension.
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Jefferson H
authors.initials: JH
authors.lastname: Amaral
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Graziele C
authors.initials: GC
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Pinheiro
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Montenegro
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil. Electronic address: tanus@fmrp.usp.br.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000633:toxicity; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D009589:Nitrogen Oxides / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012977:Sodium Nitrite / Q000494:pharmacology / Q000627:therapeutic use*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D008054:Lipid Peroxides; D009573:Nitrites; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D003900:Desoxycorticosterone; D015237:Dinoprost; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D012977:Sodium Nitrite
keywords: DOCA-salt; Hypertension; Nitric oxide; Nitrite; Oxidative stress