Component

Pig endothelial nitric oxide synthase / NOS3

Pig endothelial nitric oxide synthase / NOS3. Species, exposure and limitations are retained in each linked claim.

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

Where it participates (unsigned role)

  1. Combination treatment improved eNOS dimer ratios and NO production more than either single intervention.

    L-Citrulline plus tetrahydrobiopterin, study-specific combination → Pig pulmonary-artery eNOS dimer-to-monomer ratio source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"}
    experimental_model
    Controlled neonatal hypoxia and combination-treatment experiment
    exposure
    L-citrulline, sapropterin, or both during days 3-10 of hypoxia
    limitations
    Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Newborn pig
    plain_language
    The measured signaling machinery responded alongside the vascular outcome.
    primary_references
    [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    tissue_or_cell_type
    Pulmonary arteries and hemodynamics

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 827–838

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled neonatal hypoxia and combination-treatment experiment · source_derived_draft · unverified_draft

    ### citrulline-pig-combination-coupling Combination treatment improved eNOS dimer ratios and NO production more than either single intervention. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured signaling machinery responded alongside the vascular outcome. organism: Newborn pig tissue_or_cell_type: Pulmonary arteries and hemodynamics experimental_model: Controlled neonatal hypoxia and combination-treatment experiment limitations: Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans. exposure: L-citrulline, sapropterin, or both during days 3-10 of hypoxia evidence_span: {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"} [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    Complete structured claim and evidence

  2. Combined citrulline and BH4 improved pulmonary vascular resistance more than either alone in hypoxic piglets.

    L-Citrulline plus tetrahydrobiopterin, study-specific combination → Pulmonary vascular resistance source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"}
    experimental_model
    Controlled neonatal hypoxia and combination-treatment experiment
    exposure
    L-citrulline, sapropterin, or both during days 3-10 of hypoxia
    limitations
    Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Newborn pig
    plain_language
    Both substrate supply and cofactor support mattered in this animal model.
    primary_references
    [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    tissue_or_cell_type
    Pulmonary arteries and hemodynamics

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 814–825

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled neonatal hypoxia and combination-treatment experiment · source_derived_draft · unverified_draft

    ### citrulline-pig-combination-pvr Combined citrulline and BH4 improved pulmonary vascular resistance more than either alone in hypoxic piglets. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both substrate supply and cofactor support mattered in this animal model. organism: Newborn pig tissue_or_cell_type: Pulmonary arteries and hemodynamics experimental_model: Controlled neonatal hypoxia and combination-treatment experiment limitations: Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans. exposure: L-citrulline, sapropterin, or both during days 3-10 of hypoxia evidence_span: {"source_cache": "artifacts/citrulline-research/32073878.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f", "start_char": 0, "end_char": 1850, "text_sha256": "3362b0aae303b9c2e54cfa8a291e4d993ab4496d26cf11a1dba96c27c4c3fb7f"} [citrulline-p32073878] Combined l-citrulline and tetrahydrobiopterin therapy improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (2020). https://pubmed.ncbi.nlm.nih.gov/32073878/ DOI: 10.1152/ajplung.00280.2019
    Complete structured claim and evidence

  3. Ascorbate increased intracellular BH4 in porcine aortic endothelial cells.

    L-Ascorbate → Endothelial tetrahydrobiopterin concentration, species specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}
    experimental_model
    Cell exposure and recombinant-enzyme assays
    exposure
    Ascorbate loading; BH4 or sepiapterin comparisons
    limitations
    Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Porcine aortic endothelial cells and bovine eNOS
    plain_language
    Vitamin C can affect cofactor availability in this cell model.
    primary_references
    [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    tissue_or_cell_type
    BH4 availability and NO bioactivity

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 697–708

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell exposure and recombinant-enzyme assays · source_derived_draft · unverified_draft

    ### citrulline-vitaminc-bh4 Ascorbate increased intracellular BH4 in porcine aortic endothelial cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C can affect cofactor availability in this cell model. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    Complete structured claim and evidence

  4. Ascorbate had no additional effect at high BH4 or after sepiapterin raised cellular BH4.

    Tetrahydrobiopterin / BH4 → NOS-dependent nitric oxide production, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}
    experimental_model
    Cell exposure and recombinant-enzyme assays
    exposure
    Ascorbate loading; BH4 or sepiapterin comparisons
    limitations
    Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Porcine aortic endothelial cells and bovine eNOS
    plain_language
    The benefit depended on the starting cofactor conditions.
    primary_references
    [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    tissue_or_cell_type
    BH4 availability and NO bioactivity

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 723–734

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell exposure and recombinant-enzyme assays · source_derived_draft · unverified_draft

    ### citrulline-vitaminc-bh4-saturation Ascorbate had no additional effect at high BH4 or after sepiapterin raised cellular BH4. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The benefit depended on the starting cofactor conditions. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    Complete structured claim and evidence

  5. Ascorbate increased arginine-to-citrulline conversion and NO-related output in porcine endothelial cells.

    L-Ascorbate → NOS-dependent nitric oxide production, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}
    experimental_model
    Cell exposure and recombinant-enzyme assays
    exposure
    Ascorbate loading; BH4 or sepiapterin comparisons
    limitations
    Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Porcine aortic endothelial cells and bovine eNOS
    plain_language
    Protecting the machinery can matter as well as supplying arginine.
    primary_references
    [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    tissue_or_cell_type
    BH4 availability and NO bioactivity

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 710–721

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell exposure and recombinant-enzyme assays · source_derived_draft · unverified_draft

    ### citrulline-vitaminc-no Ascorbate increased arginine-to-citrulline conversion and NO-related output in porcine endothelial cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protecting the machinery can matter as well as supplying arginine. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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