title: Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension.
abstract: Dietary nitrite and nitrate have been reported as alternative sources of nitric oxide (NO). In this regard, we reported previously that sodium nitrite added to drinking water was able to exert antihypertensive effects in an experimental model of hypertension in a dose-dependent manner. Taking into consideration that nitrite is continuously converted to nitrate in the bloodstream, here we expanded our previous report and evaluate whether a single daily dose of sodium nitrite could exert antihypertensive effects in 2 kidney-1 clip (2K1C) hypertensive rats. Sham-operated and 2K1C rats were treated with vehicle or sodium nitrite (15 mg/kg/day) for 4 weeks. We evaluated the effects induced by sodium nitrite treatment on systolic blood pressure (SBP) and NO markers such as plasma nitrite, nitrite + nitrate (NOx), cGMP, and blood levels of nitrosyl-hemoglobin. In addition, we also evaluated effects of nitrite on oxidative stress and antioxidant enzymes. Dihydroethidium (DHE) was used to evaluate aortic reactive oxygen species (ROS) production by fluorescence microscopy, and plasma levels of thiobarbituric acid-reactive species (TBARS) were measured in plasma samples from all experimental groups. Red blood cell superoxide dismutase (SOD) and catalase activity were evaluated with commercial kits. Sodium nitrite treatment reduced SBP in 2K1C rats (P < 0.05). We found lower plasma nitrite and NOx levels in 2K1C rats compared with normotensive controls (both P < 0.05). Nitrite treatment restored the lower levels of nitrite and NOx. While no change was found in the blood levels of nitrosyl-hemoglobin (P > 0.05), nitrite treatment increased the plasma levels of cGMP in 2K1C rats (P < 0.05). Higher plasma TBARS levels and aortic ROS levels were found in hypertensive rats compared with controls (P < 0.05), and nitrite blunted these alterations. Lower SOD and catalase activities were found in 2K1C hypertensive rats compared with controls (both P < 0.05). Nitrite treatment restored SOD activity (P < 0.05), whereas catalase was not affected. These data suggest that even a single daily oral dose of sodium nitrite is able to lower SBP and exert antioxidant effects in renovascular hypertension.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil. marcelofm@pq.cnpq.br
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Montenegro
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Pinheiro
authors.forename: Jefferson H
authors.initials: JH
authors.lastname: Amaral
authors.forename: Diogo M O
authors.initials: DM
authors.lastname: Marçal
authors.forename: Ana C T
authors.initials: AC
authors.lastname: Palei
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Costa-Filho
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D006454:Hemoglobins; D009566:Nitrates; D009573:Nitrites; C008657:nitrosyl hemoglobin; D002374:Catalase; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D012977:Sodium Nitrite