Component

Pulmonary vascular remodelling

Pulmonary vascular remodelling. Species, exposure and limitations are retained in each linked claim.

3 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 acts on it

  1. PDE5 immunoreactivity was localized to smooth muscle cells in the medial layer of pulmonary arteries and veins in the normal rat lung and in distal muscularized arteries under 25 micrometres in diameter after hypoxia-induced pulmonary hypertension, sildenafil at 25 or 75 milligrams per kilogram per day given before hypoxia produced marked dose-dependent inhibition in the rise of pulmonary artery pressure of 60 to 90% and a 28.4% reduction in vascular muscularization, and when begun after 14 days of hypoxia it significantly reduced pulmonary artery pressure by 30% and partially reversed pulmonary artery muscularization by 39.9%.

    Sildenafil → Pulmonary vascular remodelling source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/12796132.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122", "start_char": 0, "end_char": 1616, "text_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122"}
    experimental_model
    Continuous telemetric pulmonary artery pressure measurement with immunolocalisation and morphometry in rats exposed to hypoxia for up to 42 days
    exposure
    Sildenafil 25 or 75 milligrams per kilogram per day started before hypoxia, or started after 14 days of established pulmonary hypertension
    limitations
    The delayed-treatment arm is what distinguishes prevention from reversal. A rat hypoxia model, and the reversal of muscularisation is partial.
    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
    Rat
    plain_language
    Started after the damage was already there, it still pushed the pressure down and partly undid the thickening.
    primary_references
    [sil-p12796132] Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12796132/ DOI: 10.1161/01.cir.0000074226.20466.b1
    tissue_or_cell_type
    Pulmonary vascular tree

    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 561–572

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Continuous telemetric pulmonary artery pressure measurement with immunolocalisation and morphometry in rats exposed to hypoxia for up to 42 days · source_derived_draft · unverified_draft

    ### sil-reverses-established-remodelling PDE5 immunoreactivity was localized to smooth muscle cells in the medial layer of pulmonary arteries and veins in the normal rat lung and in distal muscularized arteries under 25 micrometres in diameter after hypoxia-induced pulmonary hypertension, sildenafil at 25 or 75 milligrams per kilogram per day given before hypoxia produced marked dose-dependent inhibition in the rise of pulmonary artery pressure of 60 to 90% and a 28.4% reduction in vascular muscularization, and when begun after 14 days of hypoxia it significantly reduced pulmonary artery pressure by 30% and partially reversed pulmonary artery muscularization by 39.9%. Condition category: normal 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: Started after the damage was already there, it still pushed the pressure down and partly undid the thickening. organism: Rat tissue_or_cell_type: Pulmonary vascular tree experimental_model: Continuous telemetric pulmonary artery pressure measurement with immunolocalisation and morphometry in rats exposed to hypoxia for up to 42 days limitations: The delayed-treatment arm is what distinguishes prevention from reversal. A rat hypoxia model, and the reversal of muscularisation is partial. exposure: Sildenafil 25 or 75 milligrams per kilogram per day started before hypoxia, or started after 14 days of established pulmonary hypertension evidence_span: {"source_cache": "artifacts/sildenafil-research/12796132.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122", "start_char": 0, "end_char": 1616, "text_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122"} [sil-p12796132] Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12796132/ DOI: 10.1161/01.cir.0000074226.20466.b1
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Chronic hypoxia decreased RhoA messenger RNA and protein expression in rat main pulmonary artery and abolished RhoA-mediated calcium sensitisation of contraction, accounting for the decreased responses to endothelin-1, noradrenaline and a thromboxane analogue, and treatment with sildenafil at 25 milligrams per kilogram daily throughout the exposure prevented the downregulation of RhoA, the reduction of contraction and the pulmonary artery remodelling, indicating a major role of the nitric oxide and cyclic GMP pathway in the altered RhoA signalling.

    Sildenafil → RhoA and Rho-kinase-mediated calcium sensitisation of contraction source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/12946946.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ce3f4a451c01082a280ebffc7e9661ec5667161f4974b39ba15c52fa940754f7", "start_char": 0, "end_char": 1768, "text_sha256": "ce3f4a451c01082a280ebffc7e9661ec5667161f4974b39ba15c52fa940754f7"}
    experimental_model
    Rat pulmonary artery contractility and RhoA expression after two weeks of chronic hypoxia
    exposure
    Sildenafil 25 milligrams per kilogram daily through two weeks of 10 percent oxygen, with real-time PCR and western blotting
    limitations
    Identifies a second arm of the mechanism beyond cyclic-GMP-mediated relaxation. A rat chronic hypoxia model, and the causal chain from cyclic GMP to RhoA expression is inferred rather than dissected.
    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
    Rat
    plain_language
    Beyond relaxing the vessel, the drug preserved the contractile machinery that chronic low oxygen otherwise degrades.
    primary_references
    [sil-p12946946] Sildenafil prevents change in RhoA expression induced by chronic hypoxia in rat pulmonary artery. (2003). https://pubmed.ncbi.nlm.nih.gov/12946946/ DOI: 10.1161/01.res.0000093220.90027.d9
    tissue_or_cell_type
    Pulmonary artery

    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 548–559

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat pulmonary artery contractility and RhoA expression after two weeks of chronic hypoxia · source_derived_draft · unverified_draft

    ### sil-prevents-rhoa-downregulation Chronic hypoxia decreased RhoA messenger RNA and protein expression in rat main pulmonary artery and abolished RhoA-mediated calcium sensitisation of contraction, accounting for the decreased responses to endothelin-1, noradrenaline and a thromboxane analogue, and treatment with sildenafil at 25 milligrams per kilogram daily throughout the exposure prevented the downregulation of RhoA, the reduction of contraction and the pulmonary artery remodelling, indicating a major role of the nitric oxide and cyclic GMP pathway in the altered RhoA signalling. Condition category: normal 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: Beyond relaxing the vessel, the drug preserved the contractile machinery that chronic low oxygen otherwise degrades. organism: Rat tissue_or_cell_type: Pulmonary artery experimental_model: Rat pulmonary artery contractility and RhoA expression after two weeks of chronic hypoxia limitations: Identifies a second arm of the mechanism beyond cyclic-GMP-mediated relaxation. A rat chronic hypoxia model, and the causal chain from cyclic GMP to RhoA expression is inferred rather than dissected. exposure: Sildenafil 25 milligrams per kilogram daily through two weeks of 10 percent oxygen, with real-time PCR and western blotting evidence_span: {"source_cache": "artifacts/sildenafil-research/12946946.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ce3f4a451c01082a280ebffc7e9661ec5667161f4974b39ba15c52fa940754f7", "start_char": 0, "end_char": 1768, "text_sha256": "ce3f4a451c01082a280ebffc7e9661ec5667161f4974b39ba15c52fa940754f7"} [sil-p12946946] Sildenafil prevents change in RhoA expression induced by chronic hypoxia in rat pulmonary artery. (2003). https://pubmed.ncbi.nlm.nih.gov/12946946/ DOI: 10.1161/01.res.0000093220.90027.d9
    Complete structured claim and evidence

  2. 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.

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