title: Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension.
abstract: Dietary nitrite and nitrate are important sources of nitric oxide (NO). However, the use of nitrite as an antihypertensive drug may be limited by increased oxidative stress associated with hypertension. We evaluated the antihypertensive effects of sodium nitrite given in drinking water for 4 weeks in two-kidney one-clip (2K1C) hypertensive rats and the effects induced by nitrite on NO bioavailability and oxidative stress. We found that, even under the increased oxidative stress conditions present in 2K1C hypertension, nitrite reduced systolic blood pressure in a dose-dependent manner. Whereas treatment with nitrite did not significantly change plasma nitrite concentrations in 2K1C rats, it increased plasma nitrate levels significantly. Surprisingly, nitrite treatment exerted antioxidant effects in both hypertensive and sham-normotensive control rats. A series of in vitro experiments was carried out to show that the antioxidant effects induced by nitrite do not involve direct antioxidant effects or xanthine oxidase activity inhibition. Conversely, nitrite decreased vascular NADPH oxidase activity. Taken together, our results show for the first time that nitrite has antihypertensive effects in 2K1C hypertensive rats, which may be due to its antioxidant properties resulting from vascular NADPH oxidase activity inhibition.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14049-900 Ribeirao Preto, SP, Brazil. marcelofm@pq.cnpq.br
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Montenegro
authors.forename: Jefferson H
authors.initials: JH
authors.lastname: Amaral
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Pinheiro
authors.forename: Eliana K
authors.initials: EK
authors.lastname: Sakamoto
authors.forename: Graziele C
authors.initials: GC
authors.lastname: Ferreira
authors.forename: Rosana Inacio
authors.initials: RI
authors.lastname: Reis
authors.forename: Diogo M O
authors.initials: DM
authors.lastname: Marçal
authors.forename: Romaiana P
authors.initials: RP
authors.lastname: Pereira
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; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D008054:Lipid Peroxides / Q000097:blood; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000097:blood; D012977:Sodium Nitrite / Q000494:pharmacology* / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D008054:Lipid Peroxides; D009573:Nitrites; D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D012977:Sodium Nitrite