Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
Open accessAbstract
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.
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Written from the paper’s full text.
TL;DR
Sodium nitrite given in drinking water for 4 weeks reduced systolic blood pressure dose-dependently in two-kidney one-clip (2K1C) hypertensive rats despite hypertension-associated oxidative stress. The antihypertensive effect was accompanied by antioxidant effects and decreased vascular NADPH oxidase activity, without direct superoxide-scavenging by nitrite.
Key findings
- In 2K1C rats, sodium nitrite (0.5, 5, and 50 mM in drinking water for 4 weeks) significantly decreased systolic blood pressure in a dose-dependent manner (P < 0.05), while no significant SBP changes occurred in sham or sham-nitrite groups.
- Nitrite treatment did not significantly increase plasma nitrite concentrations in sham or 2K1C rats, but it dose-dependently increased plasma NOx levels in 2K1C hypertensive rats (P < 0.05); in sham rats, plasma NOx increased only with 50 mM nitrite (P < 0.05).
- Nitrite reduced oxidative stress markers: lower plasma lipid peroxide/MDA levels in both sham- and 2K1C-nitrite-treated rats versus controls (P < 0.01), lower 8-isoprostane levels in 2K1C rats at 0.5, 5, and 50 mM (P < 0.05), and attenuated aortic DHE oxidation in 2K1C rats dose-dependently (P < 0.05).
- Nitrite did not directly scavenge superoxide even at 100 μM, did not affect iron-induced lipid peroxidation, and did not decrease pyrogallol or epinephrine autoxidation (P > 0.05); however, it significantly decreased vascular NADPH oxidase activity in both sham- and 2K1C-nitrite-treated rats (P < 0.01).
Methods
- Male Wistar rats (180–200 g) underwent 2K1C hypertension induction by clipping the left renal artery with a 0.2 mm silver clip, or sham surgery; treatment began 2 weeks after surgery and continued for 4 weeks.
- Rats were randomized to vehicle or sodium nitrite at 0.5, 5, or 50 mM in drinking water (n = 12/group); estimated mean daily nitrite ingestion was approximately 5.6, 61, and 85 mg/kg for the 0.5, 5, and 50 mM groups, respectively.
- Outcomes included weekly tail-cuff systolic blood pressure, plasma NOx by Griess reaction, plasma nitrite by ozone-based reductive chemiluminescence, plasma TBARS/MDA and 8-isoprostanes, aortic DHE fluorescence, in vitro antioxidant assays, plasma xanthine oxidase activity, aortic xanthine oxidase expression by Western blotting, and aortic NADPH oxidase activity by lucigenin chemiluminescence; statistics used two-way ANOVA with Bonferroni correction or one-way ANOVA with Dunnett’s test, with P < 0.05 significant.
Limitations
- The paper states that plasma xanthine oxidase activity should be interpreted cautiously because only a trend for increased vascular xanthine oxidase expression was found, and the precise mechanism by which nitrite inhibits NADPH-induced superoxide production and which NADPH oxidase isoform is inhibited remain unclear.
- The paper also notes that DPI and apocynin are nonselective NADPH oxidase inhibitors and that apocynin may act as an antioxidant rather than an NADPH oxidase inhibitor; methemoglobin formation after nitrite treatment, especially at 50 mM, was not studied and might explain the lower weight gain in high-dose groups.
- Evident from the text: renal nitrate clearance was proposed as an explanation for differing plasma NOx responses between normotensive and hypertensive rats, but renal function/nitrate excretion was not directly measured.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
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- Findingown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
In 2K1C rats, nitrite treatment did not significantly change plasma nitrite concentrations.
“Whereas treatment with nitrite did not significantly change plasma nitrite concentrations in 2K1C rats”
- Also stated in: § Sodium nitrite treatment restored plasma NO x levels in 2K1C hypertension · plain
“Interestingly, nitrite treatment induced no significant increases in plasma nitrite concentrations in either the sham-or the 2K1C-nitrite-treated group (P N 0.05; Fig. 2B)”
Quote in the paperNot a substantial claim - Also stated in: § Sodium nitrite treatment restored plasma NO x levels in 2K1C hypertension · plain
- Findingown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
The antioxidant effects induced by nitrite do not involve xanthine oxidase activity inhibition.
“or xanthine oxidase activity inhibition.”
- Also stated in: § Sodium nitrite had small effects on plasma xanthine oxidase activity and no effects on aortic xanthine oxidase expression · plain
“treatment with nitrite induced no changes in xanthine oxidase activity in the sham groups, we found a small decrease in xanthine oxidase activity in the 2K1C nitrite 50 mM group (P b 0.05; Fig. 6A).”
Quote in the paperSubstantial claim - Also stated in: § Sodium nitrite had small effects on plasma xanthine oxidase activity and no effects on aortic xanthine oxidase expression · plain
- Findingown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
Nitrite treatment exerted antioxidant effects in both hypertensive and sham-normotensive control rats.
“Surprisingly, nitrite treatment exerted antioxidant effects in both hypertensive and sham-normotensive control rats.”
- Also stated in: § Discussion · plain
“nitrite treatment exerts antioxidant effects”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
In 2K1C rats, nitrite treatment increased plasma nitrate levels significantly.
“it increased plasma nitrate levels significantly.”
- Also stated in: § Sodium nitrite treatment restored plasma NO x levels in 2K1C hypertension · plain
“Conversely, nitrite treatment induced a dose-dependent increase in the plasma NO x levels in 2K1C hypertensive rats, as shown in Fig. 2A (P b 0.05).”
Quote in the paperNot a substantial claim - Also stated in: § Sodium nitrite treatment restored plasma NO x levels in 2K1C hypertension · plain
- Findingown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
The antioxidant effects induced by nitrite do not involve direct antioxidant effects.
“the antioxidant effects induced by nitrite do not involve direct antioxidant effects”
Quote in the paperSubstantial claim
- Findingown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
In 2K1C hypertensive rats, sodium nitrite given in drinking water for 4 weeks reduced systolic blood pressure in a dose-dependent manner, even under increased 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.”
- Also stated in: § Treatment with sodium nitrite ameliorates 2K1C hypertension in a dosedependent manner · plain
“Conversely, treatment of the 2K1C rats with nitrite induced significant decreases in SBP in all 2K1C-nitrite-treated groups in a dose-dependent manner (Fig. 1A; P b 0.05).”
- Also stated in: § Discussion · plain
“nitrite treatment reduced SBP of 2K1C hypertensive rats”
Quote in the paperSubstantial claim - Also stated in: § Treatment with sodium nitrite ameliorates 2K1C hypertension in a dosedependent manner · plain
- Findingown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
Nitrite decreased vascular NADPH oxidase activity.
“Conversely, nitrite decreased vascular NADPH oxidase activity.”
- Also stated in: § Nitrite treatment reduces the NADPH oxidase activity in 2K1C hypertension · plain
“treatment with sodium nitrite significantly decreased NADPH oxidase activity in both sham-and 2K1C-nitrite-treated rats (P b 0.01; Fig. 7A).”
- Also stated in: § Discussion · plain
“it downregulates vascular NADPH oxidase activity.”
Quote in the paperSubstantial claim - Also stated in: § Nitrite treatment reduces the NADPH oxidase activity in 2K1C hypertension · plain
- Findingown data
In sham and sham-nitrite-treated groups, no significant changes in SBP were seen.
“Whereas no significant changes in SBP were seen in the sham-and sham-nitrite-treated groups”
Quote in the paperNot a substantial claim - Findingown data
Significant increases in plasma NOx were found in sham-nitrite-treated rats only with the higher dose (50 mM).
“significant increases in plasma NO x were found in sham-nitrite-treated rats only with the higher dose (50 mM; P b 0.05; Fig. 2A).”
Quote in the paperNot a substantial claim - Findingown data
Nitrite treatment induced a dose-dependent increase in plasma NOx levels in 2K1C hypertensive rats.
“nitrite treatment induced a dose-dependent increase in the plasma NO x levels in 2K1C hypertensive rats, as shown in Fig. 2A (P b 0.05).”
Quote in the paperSubstantial claim - Findingown data
Significantly lower plasma nitrite levels were found in the 2K1C + vehicle group compared with the sham + vehicle group.
“Significantly lower plasma NO x and nitrite levels were found in the 2K1C + vehicle group compared with those found in the sham + vehicle group (P b 0.05; Figs.2A and B, respectively).”
Quote in the paperSubstantial claim - Findingown data
Nitrite treatment induced no significant increases in plasma nitrite concentrations in either the sham or the 2K1C nitrite-treated group.
“nitrite treatment induced no significant increases in plasma nitrite concentrations in either the sham-or the 2K1C-nitrite-treated group (P N 0.05; Fig. 2B)”
Quote in the paperNot a substantial claim - Findingown data
Significantly lower plasma NOx levels were found in the 2K1C + vehicle group compared with the sham + vehicle group.
“Significantly lower plasma NO x and nitrite levels were found in the 2K1C + vehicle group compared with those found in the sham + vehicle group (P b 0.05; Figs.2A and B, respectively).”
Quote in the paperSubstantial claim - Findingown data
The higher dose of nitrite tended to increase plasma nitrite levels in the 2K1C + 50 mM group.
“although the higher dose tended to increase plasma nitrite levels in the 2K1C + 50 mM group.”
Quote in the paperNot a substantial claim - Findingown data
In 2K1C groups, SBP increased after the first week of renal artery surgery and peaked at week 4 in the 2K1C + vehicle group.
“SBP increased in the 2K1C groups after the first week of the renal artery surgery and peaked at week 4 in the 2K1C + vehicle group (Fig. 1A).”
Quote in the paperSubstantial claim - Findingown data
In sham groups, nitrite treatment reduced 8-isoprostane levels when used at 0.5 and 50 mM, but not at 5 mM.
“In the sham groups, nitrite treatment reduced 8-isoprostane levels when used at 0.5 and 50 mM (P b 0.05; Fig. 3B), but not at 5 mM concentration (P N 0.05; Fig. 3B).”
Quote in the paperNot a substantial claim - Findingown data
Nitrite was unable to decrease pyrogallol and epinephrine autoxidation.
“nitrite was unable to decrease pyrogallol and epinephrine autoxidation (P N 0.05; Figs.5C and D, respectively)”
Quote in the paperSubstantial claim - Findingown data
Quercetin blunted iron-induced increases in lipid peroxidation in liver samples.
“quercetin, an antioxidant flavonoid used here as a positive control, blunted such effects (Pb 0.05; Fig. 5B).”
Quote in the paperNot a substantial claim - Findingown data
DHE oxidation was significantly increased in the 2K1C vehicle group compared to the sham groups.
“DHE oxidation was significantly increased in the 2K1C vehicle group compared to the sham groups (P b 0.05, Figs.4A and B).”
Quote in the paperSubstantial claim - Findingown data
Higher plasma 8-isoprostane levels were found in 2K1C-vehicle-treated hypertensive rats compared with sham-vehicle-treated rats.
“we found higher plasma 8-isoprostane levels in the 2K1C-vehicle-treated hypertensive rats compared with sham-vehicle-treated rats (P b 0.01; Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
Treatment with sodium nitrite significantly decreased NADPH oxidase activity in both sham- and 2K1C-nitrite-treated rats.
“treatment with sodium nitrite significantly decreased NADPH oxidase activity in both sham-and 2K1C-nitrite-treated rats (P b 0.01; Fig. 7A).”
Quote in the paperSubstantial claim - Findingown data
Preincubation of aortic slices with nitrite (0, 0.1, 1, or 10 μmol/L) for 30 min had no significant effects on DHE oxidation.
“Preincubation of aortic slices with nitrite (0, 0.1, 1, or 10 μmol/L) for 30 min had no significant effects on DHE oxidation (P N 0.05, Fig. 4C).”
Quote in the paperNot a substantial claim - Findingown data
Ascorbic acid prevented the increases in lucigenin chemiluminescence induced by pyrogallol.
“ascorbic acid was tested as a positive control and it prevented the increases in lucigenin chemiluminescence induced by pyrogallol (P b 0.05; Fig. 5A).”
Quote in the paperNot a substantial claim - Findingown data
Treatment of 2K1C rats with nitrite attenuated 2K1C-induced oxidative stress in a dose-dependent manner.
“Treatment of 2K1C rats with nitrite attenuated 2K1C-induced oxidative stress in a dose-dependent manner (P b 0.05, Figs.4A and B)”
Quote in the paperSubstantial claim - Findingown data
Increased plasma xanthine oxidase activity was found in the 2K1C vehicle group compared with the sham vehicle group.
“we found increased plasma xanthine oxidase activity in the 2K1C vehicle group compared with the sham vehicle group (P b 0.05; Fig. 6A).”
Quote in the paperNot a substantial claim - Findingown data
No effects of nitrite on oxidative stress were found in the sham-nitrite-treated groups.
“and no effects were found in the sham-nitrite-treated groups.”
Quote in the paperNot a substantial claim - Findingown data
Increased thiobarbituric acid-reactive substances (expressed as malondialdehyde) were found in the 2K1C + vehicle group compared with the sham + vehicle group.
“the results showed increased thiobarbituric acid-reactive substances (expressed in terms of malondialdehyde; MDA) in the 2K1C + vehicle group compared with the sham + vehicle group (P b 0.01; Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Treatment with sodium nitrite produced significantly lower lipid peroxide levels in both sham- and 2K1C-nitrite-treated rats compared with their respective controls.
“treatment with sodium nitrite produced antioxidant effects, as suggested by the significantly lower lipid peroxide levels in both sham-and 2K1C-nitrite-treated rats compared with their respective controls (sham + vehicle and 2K1C + vehicle group, respectively; P b 0.01; Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Nitrite had no effect on iron-induced increases in lipid peroxidation in liver samples.
“nitrite had no effect on ironinduced increases in lipid peroxidation in liver samples (PN 0.05; Fig. 5B)”
Quote in the paperSubstantial claim - Findingown data
Treatment with nitrite induced no changes in xanthine oxidase activity in the sham groups.
“treatment with nitrite induced no changes in xanthine oxidase activity in the sham groups”
Quote in the paperNot a substantial claim - Findingown data
In 2K1C hypertensive rats, nitrite treatment reduced 8-isoprostane levels when given at 0.5, 5, or 50 mM concentrations.
“nitrite treatment reduced 8-isoprostane levels when given at 0.5, 5, or 50 mM concentrations to 2K1C hypertensive rats (P b 0.05; Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
Plasma nitrite and NOx levels were lower in the 2K1C + vehicle group compared with the sham + vehicle group.
“We found lower plasma nitrite and NO x levels in the 2K1C + vehicle group compared with the sham + vehicle group”
Quote in the paperSubstantial claim - Findingown data
Treatment with nitrite did not increase nitrite levels in the sham or in the 2K1C nitrite groups.
“Treatment with nitrite did not increased nitrite levels in the sham or in the 2K1C nitrite groups”
Quote in the paperSubstantial claim - Findingown data
No changes were seen in plasma NOx levels in the sham groups.
“whereas no changes were seen in plasma NO x levels in the sham groups”
Quote in the paperSubstantial claim - Findingown data
Treatment with nitrite induced dose-dependent increases in plasma NOx levels in hypertensive rats.
“treatment with nitrite induced dose-dependent increases in plasma NO x levels in hypertensive rats.”
Quote in the paperNot a substantial claim - Findingown data
Nitrite had no direct effects on lipid peroxidation.
“Moreover, nitrite had no direct effects on lipid peroxidation.”
Quote in the paperSubstantial claim - Findingown data
Nitrite decreases blood pressure even in a context of increased oxidative stress.
“Our results show that nitrite decreases blood pressure, even in a context of increased oxidative stress.”
Quote in the paperSubstantial claim - Findingown data
Treatment with nitrite induced a small decrease in xanthine oxidase activity in the 2K1C hypertensive rats treated with the highest nitrite dose.
“treatment with nitrite induced a small decrease in xanthine oxidase activity in the 2K1C hypertensive rats treated with the highest nitrite dose.”
Quote in the paperNot a substantial claim - Findingown data
Treatment with nitrite significantly decreased vascular NADPH oxidase activity in both sham- and 2K1C-nitrite-treated rats.
“treatment with nitrite significantly decreased vascular NADPH oxidase activity in both sham-and 2K1C-nitrite-treated rats.”
- Also stated in: § Additional information · plain
“Nitrite decreases vascular NADPH oxidase activity.”
Quote in the paperSubstantial claim - Also stated in: § Additional information · plain
- Findingown data
NADPH oxidase activity was increased in 2K1C hypertensive rats treated with vehicle.
“we found increased NADPH oxidase activity in 2K1C hypertensive rats treated with vehicle.”
Quote in the paperSubstantial claim - Findingown data
Similar results were found when using nonselective NADPH oxidase inhibitors apocynin and DPI.
“Similar results were found when we used the nonselective NADPH oxidase inhibitors apocynin and DPI.”
Quote in the paperSubstantial claim - Findingown data
Treatment with nitrite decreased aortic DHE oxidation in 2K1C rats.
“we found that treatment with nitrite decreased aortic DHE oxidation in 2K1C rats”
Quote in the paperSubstantial claim - Findingown data
Nitrite itself had no direct effects on the increased aortic DHE oxidation found in hypertensive rats.
“nitrite itself had no direct effects on the increased aortic DHE oxidation found in hypertensive rats”
Quote in the paperSubstantial claim - Findingown data
Nitrite (even at 100 μM concentration) was unable to show any antioxidant effects.
“Nevertheless, nitrite (even at 100 μM concentration) was unable to show any antioxidant effects.”
Quote in the paperSubstantial claim - Findingown data
Nitrite reduced lipid peroxide levels in both sham and 2K1C rats.
“we demonstrated that nitrite reduced lipid peroxide levels in both sham and 2K1C rats”
Quote in the paperSubstantial claim - Findingown data
Xanthine oxidase activity was increased in 2K1C hypertensive rats treated with vehicle.
“we found increased xanthine oxidase activity in 2K1C hypertensive rats treated with vehicle”
Quote in the paperNot a substantial claim - Findingown data
Preincubation of aortas with tiron significantly reduced DHE oxidation.
“preincubation of aortas with tiron, a powerful direct O 2 •-scavenger, significantly reduced DHE oxidation.”
Quote in the paperSubstantial claim - Findingown data
Nitrite does not decrease pyrogallol autoxidation.
“Whereas vehicle or nitrite produced no effect, ascorbic acid significantly decreased pyrogallol autoxidation.”
Quote in the paperSubstantial claim - Findingown data
Nitrite does not decrease epinephrine autoxidation.
“shows that vehicle or nitrite does not decrease epinephrine autoxidation, whereas ascorbic acid clearly does.”
Quote in the paperSubstantial claim - Findingown data
The chemiluminescence signal is almost abolished when aortic rings are incubated with DPI, apocynin, or PEG-SOD.
“The chemiluminescence signal is almost abolished when the aortic rings are incubated for 30 min with a nonselective NADPH oxidase inhibitor, DPI (2K1C + DPI) or apocynin (2K1C + Apocynin), as well as with the cell-permeative polyethylene glycol-superoxide dismutase (2K1C+ PEG-SOD).”
Quote in the paperSubstantial claim - Findingown data
Nitrite does not scavenge O2•- generated from pyrogallol.
“Nitrite does not scavenge O 2 •-generated from pyrogallol, whereas ascorbic acid (positive control) does.”
Quote in the paperSubstantial claim - Findingown data
Nitrite does not attenuate iron-induced TBARS production in liver homogenates.
“Nitrite does not attenuate iron-induced TBARS production in liver homogenates, whereas quercetin (antioxidant, positive control) does.”
Quote in the paperNot a substantial claim - Interpretationown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
The antihypertensive effects of nitrite in 2K1C hypertensive rats may be due to its antioxidant properties resulting from vascular NADPH oxidase activity inhibition.
“which may be due to its antioxidant properties resulting from vascular NADPH oxidase activity inhibition.”
- Also stated in: § Discussion · hedged
“These findings are consistent with the idea that the overall vascular effects associated with nitrite may involve antioxidant mechanisms in addition to its bioconversion to NO.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Interpretationown data§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
Nitrite has antihypertensive effects in 2K1C hypertensive rats.
“our results show for the first time that nitrite has antihypertensive effects in 2K1C hypertensive rats”
- Also stated in: § Discussion · plain
“nitrite treatment reduced SBP of 2K1C hypertensive rats”
- Also stated in: § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension · plain
“Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension
A major feature of hypertension includes increased vascular oxidative stress.
“a major feature of hypertension includes increased vascular oxidative stress [31]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] source
Not checked in the free run.
- Interpretationown data
These data suggest that, despite increased oxidative stress present in hypertension, nitrite exerts relevant antihypertensive effects.
“These data suggest that, despite increased oxidative stress present in hypertension, nitrite exerts relevant antihypertensive effects.”
Quote in the paperSubstantial claim - Interpretationreasoning
These findings are consistent with the idea that the overall vascular effects associated with nitrite may involve antioxidant mechanisms in addition to its bioconversion to NO.
“These findings are consistent with the idea that the overall vascular effects associated with nitrite may involve antioxidant mechanisms in addition to its bioconversion to NO.”
Quote in the paperSubstantial claim - Premisecitation
Classen et al. found that a single oral dose of nitrite acutely decreased blood pressure in spontaneously hypertensive rats.
“They found that a single oral dose of nitrite acutely decreased blood pressure in spontaneously hypertensive rats (SHR) [26].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [26] source
Not checked in the free run.
- Interpretationown data
Hypertension decreases NO availability.
“thus suggesting that hypertension decreases NO availability.”
Quote in the paperSubstantial claim - Premisecitation
NO donors may have toxic effects resulting from the reaction between superoxide anion and NO released by these drugs, forming peroxynitrite.
“NO donors may have toxic effects resulting from the reaction between superoxide anion and NO released by these drugs, thus forming peroxynitrite [49].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [49] source
Not checked in the free run.
- Interpretationown data
This is the first study clearly showing antihypertensive effects exerted by nitrite in 2K1C hypertensive rats.
“To our knowledge, this is the first study clearly showing antihypertensive effects exerted by nitrite in 2K1C hypertensive rats.”
Quote in the paperSubstantial claim - Interpretationreasoning
Nitrite may offer some advantages in the treatment of hypertension compared with other NO-donor drugs, especially in a context of increased oxidative stress.
“Our findings suggest that nitrite may offer some advantages in the treatment of hypertension compared with other NO-donor drugs, especially in a context of increased oxidative stress.”
Quote in the paperSubstantial claim - Interpretationown data
The differences in plasma NOx levels found between normotensive and hypertensive rats suggest that the kinetic profiles of nitrite/nitrate are different in normotensive versus hypertensive animals.
“The differences in plasma NO x levels found between normotensive and hypertensive rats reported here suggest that the kinetic profiles of nitrite/nitrate are different in normotensive versus hypertensive animals.”
Quote in the paperNot a substantial claim - Premisecitation
High concentrations of oxyhemoglobin usually found in the bloodstream can easily convert nitrite to nitrate.
“the high concentrations of oxyhemoglobin usually found in the bloodstream can easily convert nitrite to nitrate [47,48].”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
The results rule out the possibility that nitrite could have direct antioxidant effects.
“Overall, our results provide strong evidence ruling out the possibility that nitrite could have direct antioxidant effects.”
Quote in the paperSubstantial claim - Interpretationown data
Nitrite has antioxidant effects.
“thus suggesting antioxidant effects produced by this compound.”
- Also stated in: § Discussion · plain
“Together, these findings are consistent with antioxidant effects exerted by nitrite.”
- Also stated in: § Discussion · hedged
“In conclusion, our results show evidence that nitrite has antioxidant effects, probably explained by NADPH oxidase downregulation.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Premisecitation
Nitrite has antioxidant effects in an animal model of acute pulmonary thromboembolism.
“we have previously shown antioxidant effects exerted by nitrite in an animal model of acute pulmonary thromboembolism [21,23].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [21]
Not checked in the free run.
- cites [23] source
Not checked in the free run.
- Interpretationown data
Nitrite exerts relevant antioxidant effects by inhibiting vascular NADPH oxidase activity.
“These results, together with the lower lipid peroxide levels and decreased aortic DHE oxidation in 2K1C rats treated with nitrite, are consistent with the suggestion that nitrite exerts relevant antioxidant effects by inhibiting vascular NADPH activity.”
Quote in the paperSubstantial claim - Premisecitation
Nitrite reduced the production of superoxide by neutrophils stimulated with phorbol 12-myristate 13-acetate, an NADPH oxidase activator.
“nitrite reduced the production of superoxide by neutrophils stimulated with phorbol 12-myristate 13acetate, an NADPH oxidase activator [21].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21]
Not checked in the free run.
- Interpretationown data
In addition to its vasodilator properties, nitrite may have relevant antioxidant effects that contribute to its antihypertensive effects.
“our findings underscore the notion that, in addition to its vasodilator properties, nitrite may have relevant antioxidant effects that contribute to its antihypertensive effects reported here.”
Quote in the paperSubstantial claim - Interpretationreasoning
The findings show a new and relevant mechanism for the antihypertensive properties of nitrite in 2K1C hypertensive rats.
“Our findings show a new and relevant mechanism for the antihypertensive properties of nitrite in 2K1C hypertensive rats.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 27
- May combine two claims. 20
- The quote only partly states this claim. 1
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThe average drinking water consumption was 68 ± 11 ml/rat/day in groups receiving only water or nitrite at 0.5 and 5 mM in the drinking water.
“the average drinking water consumption was 68 ± 11 ml/rat/day in groups receiving only water or nitrite at 0.5 and 5 mM in the drinking water.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataGroups of rats receiving nitrite at 50 mM had a 37% lower drinking water consumption.
“we found a 37% lower consumption in the groups of rats receiving nitrite at 50 mM.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNo significant differences in body weight were found when all experimental groups were compared, except that both sham and 2K1C groups receiving 50 mM nitrite gained less weight than the other groups.
“We found no significant differences in body weight when all the experimental groups were compared (Fig. 1B, P N 0.05), except for both sham and 2K1C groups receiving 50 mM nitrite, which gained less weight than the other groups (Fig. 1B, P b 0.05).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe analysis of xanthine oxidase expression in the aortas showed a trend for increased xanthine oxidase expression in 2K1C hypertensive rats compared with sham animals, but this was not significant.
“The analysis of xanthine oxidase expression in the aortas showed a trend for increased xanthine oxidase expression in 2K1C hypertensive rats compared with sham animals (P N 0.05; Fig. 6B)”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataNitrite had no significant effects on aortic xanthine oxidase expression.
“and no significant effects for nitrite.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataA small decrease in xanthine oxidase activity was found in the 2K1C nitrite 50 mM group.
“we found a small decrease in xanthine oxidase activity in the 2K1C nitrite 50 mM group (P b 0.05; Fig. 6A).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataAscorbic acid prevented both pyrogallol and epinephrine autoxidation.
“ascorbic acid was used as a positive control and it prevented both pyrogallol and epinephrine autoxidation (P b 0.05; Figs.5C and D, respectively).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThere was a trend for increased nitrite levels with the higher nitrite dose in the 2K1C + nitrite 50 mM group.
“despite a trend for increased nitrite levels with the higher nitrite dose in the 2K1C + nitrite 50 mM group.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn the present study, treatment with nitrite produced significant antihypertensive effects after the first week of treatment, and this effect improved with time.
“Interestingly, we found significant antihypertensive effects after the first week of treatment, and this effect improved with time.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataWe found only a trend for increased xanthine oxidase expression.
“we found only a trend for increased expression.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAllopurinol or rotenone had no effects on the chemiluminescence signal.
“However, the xanthine oxidase inhibitor allopurinol (2K1C + Allopurinol) or the inhibitor of mitochondrial electron transport rotenone (2K1C + Rotenone) had no effects.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionNitrite reduction to NO involves mechanisms including pH-dependent reduction in the stomach, reduction by xanthine oxidase, deoxyhemoglobin, myoglobin, cytochrome P450, and enzymes of the mitochondrial respiratory chain.
“The mechanisms involved in nitrite reduction to NO include pH-dependent reduction in the stomach [9,10] or reduction by xanthine oxidase [11,12], deoxyhemoglobin [13], myoglobin [14,15], cytochrome P450 [16], and enzymes of the mitochondrial respiratory chain [17].”
Quote in the paperNot a substantial claim0 of 5 sources checkedClassified as probably not a substantial claim.
Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionNitrite and nitrate can be recycled back to NO rather than being inert end products of NO.
“more recent studies showed that, rather than being inert end products of NO, nitrite and nitrate can be recycled back to NO [7,8].”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionNitrite and nitrate are products of the L-arginine-NO synthase pathway.
“Nitrite and nitrate are now known as products of the L-arginine-NO synthase pathway [3]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionThe blood-pressure-lowering effects of nitrate in healthy humans were ascribed to nitrate bioconversion to nitrite, which ultimately generates NO.
“these effects were ascribed to nitrate bioconversion to nitrite, which ultimately generates NO [28,30].”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Study design and conductown dataBaseline SBP and body weight were similar in all experimental groups.
“Baseline SBP and body weight were similar in all experimental groups (Figs.1A and B).”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionIncreased vascular oxidative stress decreases NO bioavailability and contributes to the formation of peroxynitrite, a highly oxidant molecule.
“which decreases NO bioavailability and also contributes to the formation of peroxynitrite, a highly oxidant molecule [32].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionInorganic nitrate supplementation, as well as a nitrate-rich meal, reduced blood pressure in healthy humans.
“inorganic nitrate supplementation, as well as a nitraterich meal, reduced blood pressure in healthy humans [28,30]”
Quote in the paperSubstantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
Premisereasoning§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionIt is not clear whether nitrite could be used in the therapy of hypertension.
“Therefore, it is not clear whether nitrite could be used in the therapy of hypertension.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Premisecitation§ Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertensionNitrite or nitrate have been associated with beneficial effects including protection against ischemia-reperfusion injury, vasorelaxant properties, pulmonary vasodilator effects, and antihypertensive effects in experimental and clinical studies.
“relevant biological effects were associated with nitrite or nitrate, including beneficial effects against ischemia-reperfusion injury [11,18,19], vasorelaxant properties [20], pulmonary vasodilator effects [21][22][23], and antihypertensive effects in experimental [24][25][26][27] and in clinical studies [28][29][30].”
Quote in the paperSubstantial claim0 of 5 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenThe effect of nitrite in hypertension has been poorly studied.
“However, the effect of nitrite in hypertension has been poorly studied.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationIron increases lipid peroxidation in tissue homogenates, which can be prevented by antioxidants.
“The rationale for these experiments is that iron increases lipid peroxidation in the tissue homogenates, which can be prevented by antioxidants [41].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNitrite produces vasodilator effects, which are ascribed to nitric oxide formation.
“Several reports have described vasodilator effects produced by nitrite, which are ascribed to nitrite oxide formation [8].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataThe standard curve measurements of nitrate and nitrite showed a strong correlation (R = 0.999), and the recovery of nitrite was ~98%.
“We found a strong correlation between the standard curve measurements of nitrate and nitrite (R = 0.999), and the recovery of nitrite was ~98% (data not shown).”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThe chemiluminescence signal was suppressed by PEG-SOD and by the nonselective NADPH oxidase inhibitors DPI and apocynin, indicating that the signal was not an artifact.
“the chemiluminescence signal was suppressed by PEG-SOD and by the nonselective NADPH oxidase inhibitors DPI and apocynin, thus indicating that the signal was not an artifact (P b 0.01; Fig. 7B).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims. The quote only partly states this claim.
Study design and conductown dataSham-operated and 2K1C rats were randomly divided into four groups.
“The sham-operated rats were randomly divided into four groups (n = 12/group)”
- Also stated in: § Animals and treatments · plain
“Similarly, the 2K1C rats were randomly divided into four groups (n = 12/group)”
Quote in the paperSubstantial claim- Also stated in: § Animals and treatments · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningTo minimize the effects of stress induced by tail-cuff plethysmography on blood pressure measurement, the animals were trained for a week before surgery.
“To minimize the effects of stress induced by this method on blood pressure measurement, the animals were trained for a week before surgery.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataXanthine oxidase and mitochondria are not relevant contributors to superoxide production.
“the pretreatment of aortic rings with allopurinol or rotenone had no effect on NADPH-induced superoxide production (P N 0.05; Fig. 7B), thus suggesting that xanthine oxidase and mitochondria are not relevant contributors to superoxide production.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe assay results were not significantly affected by the presence of plasma proteins.
“The assay results were not significantly affected by the presence of plasma proteins.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataNitrite is continuously converted to nitrate and supplying more nitrite results only in its oxidation to nitrate.
“Together, these findings suggest that nitrite is continuously converted to nitrate and that supplying more nitrite results only in its oxidation to nitrate.”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTsuchiya et al. showed that nitrite attenuated the increases in blood pressure caused by L-NAME, an inhibitor of NO synthases.
“In parallel with these findings, Tsuchiya et al. showed that nitrite attenuated the increases in blood pressure caused by L-NAME, an inhibitor of NO synthases [46].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [46] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLater, the same group showed that nitrite attenuated further increases in systolic blood pressure in SHR.
“Later, the same group showed that nitrite attenuated further increases in SBP found in SHR [44,45].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [44]
Not checked in the free run.
- cites [45]
Not checked in the free run.
May combine two claims.
PremisecitationIn those studies, nitrite did not decrease blood pressure, although it prevented further increases in blood pressure found in matched controls treated with water.
“Interestingly, nitrite did not decrease blood pressure in these studies, although it prevented further increases in blood pressure found in matched controls treated with water [45].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45]
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationBoth xanthine oxidase and NADPH oxidase have been implicated as important prooxidant enzymes contributing to hypertension.
“Both enzymes have been implicated as important prooxidant enzymes contributing to hypertension [32,50,51].”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationNitrite infusions attenuated the pulmonary hypertension caused by acute pulmonary thromboembolism, and this effect was associated with lower lipid peroxidation.
“Nitrite infusions attenuated the pulmonary hypertension caused by acute pulmonary thromboembolism and this effect was associated with lower lipid peroxidation [21,23].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [21]
Not checked in the free run.
- cites [23] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationApocynin may have antioxidant effects rather than being an NADPH oxidase inhibitor.
“Apocynin may have antioxidant effects rather than being an NADPH oxidase inhibitor [52].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [52] source
Not checked in the free run.
May combine two claims.
Interpretationown dataNitrite has antioxidant effects, probably explained by NADPH oxidase downregulation.
“In conclusion, our results show evidence that nitrite has antioxidant effects, probably explained by NADPH oxidase downregulation.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationown dataThe increased xanthine oxidase activity in vascular tissues could help to explain the effects exerted by nitrite in this study.
“However, the increased xanthine oxidase activity in vascular tissues could help to explain the effects exerted by nitrite in this study.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIncreased xanthine oxidase expression has been reported in hypertension.
“Although increased xanthine oxidase expression has been reported in hypertension [42]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [42] source
Not checked in the free run.
The paper relies on this without support.
NADPH oxidase is an important pro-oxidant enzyme, especially in hypertension.
“we decided to study vascular NADPH oxidase activity because this is an important pro-oxidant enzyme, especially in hypertension.”
The paper relies on this without support.
2K1C hypertensive rats have impaired renal function and therefore lower renal nitrate clearance, whereas normotensive rats do not have this alteration.
“2K1C hypertensive rats have impaired renal function and therefore lower renal nitrate clearance, whereas normotensive rats do not have this alteration.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In liver homogenates, nitrite administration does not exert direct antioxidant effects.
“nitrite administration did not exert direct antioxidant effects”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [128]
In hypertensive rats, nitrite supplementation reduces staining for superoxide in aortic rings.
“recent findings in hypertensive rats showing reduced staining for superoxide in aortic rings following nitrite supplementation (128, 129)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [128]
In liver homogenates, nitrite administration does not suppress mitochondrial superoxide production.
“suppress mitochondrial superoxide production”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [128]
Nitrite appears to exert its antioxidant influence via inhibition of NADPH oxidase protein expression and activity.
“but rather appeared to exert its antioxidant influence via inhibition of NADPH oxidase protein expression and activity (128)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [128]
In liver homogenates, nitrite administration does not inhibit xanthine oxidase.
“inhibit the oxidant enzyme xanthine oxidase”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [128]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Discussion denies a reported increase in sham plasma NOx
MajorThe results report a significant plasma NOx increase in sham rats at 50 mM nitrite, but the discussion says there were no changes in the sham groups.
“However, significant increases in plasma NO x were found in sham-nitrite-treated rats only with the higher dose (50 mM; P b 0.05; Fig. 2A).”
“Conversely, whereas no changes were seen in plasma NO x levels in the sham groups, treatment with nitrite induced dose-dependent increases in plasma NO x levels in hypertensive rats.”
Reported intake at 50 mM is inconsistent with concentration and water consumption
MajorThe 50 mM solution is ten times as concentrated as the 5 mM solution, while the reported 37% reduction in water consumption would make the ingested amount about 6.3 times as large. Instead, the reported doses are 85 versus 61 mg/kg-only about 1.4 times as large-even though the 50 mM groups gained less weight.
“The calculated mean daily nitrite ingestion resulted in approximately 5.6, 61, and 85 mg/kg of nitrite in the groups treated with 0.5, 5, and 50 mM nitrite in their drinking water, respectively.”
“Interestingly, the average drinking water consumption was 68 ± 11 ml/rat/day in groups receiving only water or nitrite at 0.5 and 5 mM in the drinking water.However, we found a 37% lower consumption in the groups of rats receiving nitrite at 50 mM.”
Aortic-slice nitrite preincubation is reported as both 30 and 20 minutes
MinorThe results specify a 30-minute preincubation for the aortic-slice nitrite experiment, whereas the caption for that experiment specifies 20 minutes.
“Preincubation of aortic slices with nitrite (0, 0.1, 1, or 10 μmol/L) for 30 min had no significant effects on DHE oxidation (P N 0.05, Fig. 4C).”
“(C) The effects induced by pretreatment of aortic slices (for 20 min) with vehicle or increasing concentrations of nitrite on DHE oxidation.”
The citation lists haven’t been fetched yet
References 56 · Cited by 152
- Authors
- Montenegro, M. F., Amaral, J. H., Pinheiro, L. C., Sakamoto, E. K., Ferreira, G. C., Reis, R. I., Marçal, D. M. O., Pereira, R. P., & Tanus-Santos, J. E.
- Affiliations
- Universidade de São Paulo (BR)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Universidade Federal de São Paulo (BR)
- Universidade Federal de Santa Maria (BR)
- Corresponding author
- Montenegro, Marcelo F.
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 51
- Issue
- 1
- Pages
- 144-152
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2094077539
- Semantic Scholar
- 07a4f0c7efcbe429b1e011c5f6232a73a344d9c6
- Cited by
- 152
- References
- 56
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 12 · 2020: 8 · 2019: 11 · 2018: 21 · 2017: 12 · 2016: 15 · 2015: 13 · 2014: 13 · 2013: 8 · 2012: 11
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- sodium nitrite, hypertension, NADPH oxidase, antihypertensive effect, oxidative stress, nitric oxide bioavailability, nitrate, antioxidant activity, two-kidney one-clip model, xanthine oxidase
- MeSH terms
- Animals, Antihypertensive Agents, Antioxidants, Blood Pressure, Hypertension, Lipid Peroxides, Nitric Oxide, Nitrites, Sodium Nitrite, Xanthine Oxidase, Dinoprost, Down-Regulation, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Rats
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