ArticleCardiovascular research2020
Long-lasting blood pressure lowering effects of nitrite are NO-independent and mediated by hydrogen peroxide, persulfides, and oxidation of protein kinase G1α redox signalling.
Article in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Nitrate ingestion blunts the increase in blood pressure during cool air exposure: a double-blind, placebo-controlled, randomized, crossover trial.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Trial
- Influence of acute dietary nitrate supplementation timing on nitrate metabolism, central and peripheral blood pressure and exercise tolerance in young men.European journal of applied physiology · 2024Trial
- Effects of dietary nitrate supplementation on microvascular physiology at 4559 m altitude - A randomised controlled trial (Xtreme Alps).Nitric oxide : biology and chemistry · 2020Trial
- Hydropersulfides promote angiogenesis and preserve vascular function.Redox biology · 2026Article
- Nitrite increases mitofusin-1 levels to inhibit vascular smooth muscle cell proliferation and prevent intimal hyperplasia.Redox biology · 2026Article
- Sodium nitrite reduces circulating asymmetric dimethylarginine in a reduced uterine perfusion pressure rat model of preeclampsia.Frontiers in pharmacology · 2026Article
- The effects of major abdominal surgery on skeletal muscle mitochondrial respiration in relation to systemic redox status and cardiopulmonary fitness.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- The Role of Oxidative Stress in Hypertension: The Insight into Antihypertensive Properties of Vitamins A, C and E.Antioxidants (Basel, Switzerland) · 2024Review
- Vascular dysfunction caused by loss of Brn-3b/POU4F2 transcription factor in aortic vascular smooth muscle cells is linked to deregulation of calcium signalling pathways.Cell death & disease · 2023Article
- Orally administered sodium nitrite prevents the increased α-1 adrenergic vasoconstriction induced by hypertension and promotes the S-nitrosylation of calcium/calmodulin-dependent protein kinase II.Biochemical pharmacology · 2023Article
- Soluble guanylate cyclase activator BAY 54-6544 improves vasomotor function and survival in an accelerated ageing mouse model.Aging cell · 2022Article
- A physiologically relevant role for NO stored in vascular smooth muscle cells: A novel theory of vascular NO signaling.Redox biology · 2022Review
- U-shaped association of uric acid to overall-cause mortality and its impact on clinical management of hyperuricemia.Redox biology · 2022Review
- Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide.International journal of molecular sciences · 2022Review
- The Footprint of Kynurenine Pathway in Cardiovascular Diseases.International journal of tryptophan research : IJTR · 2022Review
- The Use of Wire Myography to Investigate Vascular Tone and Function.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Exercise Training Induces a Shift in Extracellular Redox Status with Alterations in the Pulmonary and Systemic Redox Landscape in Asthma.Antioxidants (Basel, Switzerland) · 2021Article
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
- Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Oxidative Stress: A Unifying Paradigm in Hypertension.The Canadian journal of cardiology · 2020Review
Corrections and comments
- Commented on by
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
aimsUnder hypoxic conditions, nitrite (NO2-) can be reduced to nitric oxide (NO) eliciting vasorelaxation. However, nitrite also exerts vasorelaxant effects of potential therapeutic relevance under normal physiological conditions via undetermined mechanisms. We, therefore, sought to investigate the mechanism(s) by which nitrite regulates the vascular system in normoxia and, specifically, whether the biological effects are a result of NO generation (as in hypoxia) or mediated via alternative mechanisms involving classical downstream targets of NO [e.g. effects on protein kinase G1α (PKG1α)]. METHODS AND
resultsEx vivo myography revealed that, unlike in thoracic aorta (conduit vessels), the vasorelaxant effects of nitrite in mesenteric resistance vessels from wild-type (WT) mice were NO-independent. Oxidants such as H2O2 promote disulfide formation of PKG1α, resulting in NO- cyclic guanosine monophosphate (cGMP) independent kinase activation. To explore whether the microvascular effects of nitrite were associated with PKG1α oxidation, we used a Cys42Ser PKG1α knock-in (C42S PKG1α KI; 'redox-dead') mouse that cannot transduce oxidant signals. Resistance vessels from these C42S PKG1α KI mice were markedly less responsive to nitrite-induced vasodilation. Intraperitoneal (i.p.) bolus application of nitrite in conscious WT mice induced a rapid yet transient increase in plasma nitrite and cGMP concentrations followed by prolonged hypotensive effects, as assessed using in vivo telemetry. In the C42S PKG1α KI mice, the blood pressure lowering effects of nitrite were lower compared to WT. Increased H2O2 concentrations were detected in WT resistance vessel tissue challenged with nitrite. Consistent with this, increased cysteine and glutathione persulfide levels were detected in these vessels by mass spectrometry, matching the temporal profile of nitrite's effects on H2O2 and blood pressure.
conclusionUnder physiological conditions, nitrite induces a delayed and long-lasting blood pressure lowering effect, which is NO-independent and occurs via a new redox mechanism involving H2O2, persulfides, and PKG1α oxidation/activation. Targeting this novel pathway may provide new prospects for anti-hypertensive therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.