Component

Experimental endothelial nitric oxide synthase knockout mouse genotype

Experimental endothelial nitric oxide synthase knockout mouse genotype. Species, exposure and limitations are retained in each linked claim.

2 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

What it acts on

  1. Stem cell mobilisation did not occur in knockout mice lacking genes for endothelial nitric oxide synthase, and pretreatment of wild-type mice with a nitric oxide synthase inhibitor prevented the elevation in stem cell factor and circulating stem cells.

    Experimental endothelial nitric oxide synthase knockout mouse genotype → Circulating CD34-positive stem and progenitor cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"}
    experimental_model
    Human volunteers, mice, and endothelial nitric oxide synthase knockout mice
    exposure
    2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments
    limitations
    The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel.
    nutrient_topic
    Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy
    organism
    Human and mouse
    plain_language
    Remove the enzyme that makes nitric oxide and the cells stay in the marrow.
    primary_references
    [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005
    tissue_or_cell_type
    Bone marrow and peripheral blood
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 569–580

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human volunteers, mice, and endothelial nitric oxide synthase knockout mice · source_derived_draft · unverified_draft

    ### hbot-nos3-required Stem cell mobilisation did not occur in knockout mice lacking genes for endothelial nitric oxide synthase, and pretreatment of wild-type mice with a nitric oxide synthase inhibitor prevented the elevation in stem cell factor and circulating stem cells. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Remove the enzyme that makes nitric oxide and the cells stay in the marrow. organism: Human and mouse tissue_or_cell_type: Bone marrow and peripheral blood experimental_model: Human volunteers, mice, and endothelial nitric oxide synthase knockout mice limitations: The knockout and inhibitor arms carry the causal claim. Progenitor phenotype is defined by surface markers and colony formation, not by a demonstrated contribution to a healed vessel. exposure: 2.0 atmospheres absolute oxygen for 2 hours, single and over 20 treatments evidence_span: {"source_cache": "artifacts/hbot-research/16299259.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730", "start_char": 0, "end_char": 1502, "text_sha256": "76c0554557a30ac9a32f25b74b27edb5f8f8a57ee0c0660dfe5619b78732c730"} [hbot-p16299259] Stem cell mobilization by hyperbaric oxygen. (2006). https://pubmed.ncbi.nlm.nih.gov/16299259/ DOI: 10.1152/ajpheart.00888.2005
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. In isolated perfused lung of wild-type and endothelial nitric oxide synthase deficient mice sildenafil markedly blunted acute hypoxic pulmonary vasoconstriction, wild-type mice dosed through three weeks of hypoxia showed a significant reduction in right ventricular systolic pressure from 43.3 to 29.9 millimetres of mercury coupled with a small reduction in right ventricular hypertrophy and inhibition of pulmonary vascular remodelling, while in the knockout mice the drug attenuated the rise in right ventricular systolic pressure but without significant effect on hypertrophy or remodelling, so the endothelial pathway contributes but other biochemical sources of cyclic GMP also play a role.

    Sildenafil → Hypoxic pulmonary vasoconstriction source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/11468204.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "41d880663288811422c4400d86de1eedd4d5b254d8bb3a59a8fbff01dedbcb24", "start_char": 0, "end_char": 1820, "text_sha256": "41d880663288811422c4400d86de1eedd4d5b254d8bb3a59a8fbff01dedbcb24"}
    experimental_model
    Randomised double-blind hypoxic challenge in ten volunteers with right heart catheterisation, plus isolated perfused lung and chronic hypoxia in wild-type and endothelial nitric oxide synthase deficient mice
    exposure
    Sildenafil 100 milligrams orally before 11 percent oxygen for 30 minutes, and 25 milligrams per kilogram daily through three weeks of 10 percent oxygen in mice
    limitations
    The knockout arm is what makes this decisive about the source of cyclic GMP, and the human arm measures pressure invasively. Ten volunteers, and the mouse exposure is far longer than the human one.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Mouse
    plain_language
    It still works when the main source of the upstream signal has been deleted, so something else is supplying the messenger.
    primary_references
    [sil-p11468204] Sildenafil inhibits hypoxia-induced pulmonary hypertension. (2001). https://pubmed.ncbi.nlm.nih.gov/11468204/ DOI: 10.1161/hc2901.093117
    tissue_or_cell_type
    Pulmonary circulation
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 509–520

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised double-blind hypoxic challenge in ten volunteers with right heart catheterisation, plus isolated perfused lung and chronic hypoxia in wild-type and endothelial nitric oxide synthase deficient mice · source_derived_draft · unverified_draft

    ### sil-works-without-enos In isolated perfused lung of wild-type and endothelial nitric oxide synthase deficient mice sildenafil markedly blunted acute hypoxic pulmonary vasoconstriction, wild-type mice dosed through three weeks of hypoxia showed a significant reduction in right ventricular systolic pressure from 43.3 to 29.9 millimetres of mercury coupled with a small reduction in right ventricular hypertrophy and inhibition of pulmonary vascular remodelling, while in the knockout mice the drug attenuated the rise in right ventricular systolic pressure but without significant effect on hypertrophy or remodelling, so the endothelial pathway contributes but other biochemical sources of cyclic GMP also play a role. Condition category: machinery_impairment nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: It still works when the main source of the upstream signal has been deleted, so something else is supplying the messenger. organism: Mouse tissue_or_cell_type: Pulmonary circulation experimental_model: Randomised double-blind hypoxic challenge in ten volunteers with right heart catheterisation, plus isolated perfused lung and chronic hypoxia in wild-type and endothelial nitric oxide synthase deficient mice limitations: The knockout arm is what makes this decisive about the source of cyclic GMP, and the human arm measures pressure invasively. Ten volunteers, and the mouse exposure is far longer than the human one. exposure: Sildenafil 100 milligrams orally before 11 percent oxygen for 30 minutes, and 25 milligrams per kilogram daily through three weeks of 10 percent oxygen in mice evidence_span: {"source_cache": "artifacts/sildenafil-research/11468204.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "41d880663288811422c4400d86de1eedd4d5b254d8bb3a59a8fbff01dedbcb24", "start_char": 0, "end_char": 1820, "text_sha256": "41d880663288811422c4400d86de1eedd4d5b254d8bb3a59a8fbff01dedbcb24"} [sil-p11468204] Sildenafil inhibits hypoxia-induced pulmonary hypertension. (2001). https://pubmed.ncbi.nlm.nih.gov/11468204/ DOI: 10.1161/hc2901.093117
    Complete structured claim and evidence

In the sources

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

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards