Cited by 152Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionBlood Pressure and Hypertension Studies

Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

Open access
Montenegro, Marcelo F., Amaral, Jefferson H., Pinheiro, Lucas C., Sakamoto, Eliana K., Ferreira, Graziele C., Reis, Rosana Inacio, Marçal, Diogo M.O., Pereira, Romaiana P. +1 more·2011·Free Radical Biology and Medicine

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.

AI snapshot

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.

Integrity signals

Registry

Crossref · 10.1016/j.freeradbiomed.2011.04.005

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 data

    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.

    “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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Groups 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 claim
  • May combine two claims.

    Findingown data

    No 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 claim
  • May combine two claims.

    Findingown data

    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, 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Nitrite had no significant effects on aortic xanthine oxidase expression.

    “and no significant effects for nitrite.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    A 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Ascorbic 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There 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 claim
  • May combine two claims.

    Findingown data

    In 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    We found only a trend for increased xanthine oxidase expression.

    “we found only a trend for increased expression.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Allopurinol 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    Nitrite 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 checked
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  • Classified as probably not a substantial claim.

    Premisecitation
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    Nitrite 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 checked
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    Premisecitation
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    Nitrite 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

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    The 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 checked
    • cites [28] source

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  • May combine two claims.

    Study design and conductown data

    Baseline 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 claim
  • May combine two claims.

    Premisecitation
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    Increased 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

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    Inorganic 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 checked
    • cites [28] source

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  • Classified as probably not a substantial claim.

    Premisereasoning
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    It 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 claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

    Nitrite 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 checked
    • cites [11] source

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    • cites [21][22][23]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The 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 claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Iron 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

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Nitrite 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

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The 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 claim
  • May combine two claims.

    Study design and conductown data

    The 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 claim
  • Classified as probably not a substantial claim. May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    Sham-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
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    To 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 claim
  • May combine two claims.

    Interpretationown data

    Xanthine 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The 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 claim
  • May combine two claims.

    Interpretationown data

    Nitrite 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 checked
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    • cites [43] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Tsuchiya 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
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Later, 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
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    Premisecitation

    In 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]

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Both 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 checked
    • cites [32] source

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  • May combine two claims.

    Premisecitation

    Nitrite 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]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Apocynin 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

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  • May combine two claims.

    Interpretationown data

    Nitrite 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    The 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 claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increased 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

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39 of 39
  • 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.”
2 of 2

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?

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

    Major

    The 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.

  • Reported intake at 50 mM is inconsistent with concentration and water consumption

    Major

    The 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.

  • Aortic-slice nitrite preincubation is reported as both 30 and 20 minutes

    Minor

    The results specify a 30-minute preincubation for the aortic-slice nitrite experiment, whereas the caption for that experiment specifies 20 minutes.

3 of 3

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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.
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
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
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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