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.

Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats

“…Interestingly, it was shown that nitrite instillation in the jejunum decreased arterial blood pressure when NO-Hb achieved 10 mM concentration, and this was suggested as a level required for initiating vasorelaxation, even though the authors did not provide evidence that the hypotension was due to NO release from NO-Hb [42]. In addition, we found no significant increase in NO-Hb concentrations in rats treated with nitrite at 15 mg/kg for 4 weeks in a previous study [43]. Notwithstanding these criticisms, we believe that our findings are of major importance and very consistent.…”

Acute oral dose of sodium nitrite induces redox imbalance, DNA damage, metabolic and histological changes in rat intestine

“…Although antioxidant property of NaNO 2 at low doses has been reported, it does not act as a direct antioxidant. Montenegro et al [61] have shown the inability of nitrite to scavenge superoxide radicals or ameliorate iron-induced lipid peroxidation under in vitro conditions. The reported cellular antioxidant effect can probably be explained by NADPH oxidase downregulation and/or alterations in activities of enzymes involved in antioxidant defense [62,63].…”

Salivary, blood and plasma nitrite concentrations in periodontal patients and healthy individuals before and after periodontal treatment

“…Nitrite concentrations in the samples were determined using a previously described ozone-based reductive chemiluminescence assay [23]. First, saliva samples were diluted in ultrapure water, to obtain a 5% solution of stimulated whole saliva and 50% solution of submandibular and parotid saliva.…”