Hypoxic pulmonary vasoconstriction: molecular mechanisms & dependencies

How nutrients influence it

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Human evidence only

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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

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

Where it participates (unsigned role)

In a randomised double-blind study the acute 56% increase in mean pulmonary artery pressure produced by breathing 11 percent oxygen during placebo treatment, from 16.0 to 25.0 millimetres of mercury, was almost abolished by sildenafil 100 milligrams, from 16.0 to 18.0 millimetres of mercury, with no significant effect on systemic blood pressure.
Sildenafil → Mean or systolic pulmonary artery pressure source_derived_draftungraded
Experimental context and source evidence
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
Human and mouse
plain_language
A single dose almost removed the pressure rise that low oxygen causes in the lung, without touching pressure elsewhere.
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
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 522–533
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-abolishes-the-hypoxic-rise In a randomised double-blind study the acute 56% increase in mean pulmonary artery pressure produced by breathing 11 percent oxygen during placebo treatment, from 16.0 to 25.0 millimetres of mercury, was almost abolished by sildenafil 100 milligrams, from 16.0 to 18.0 millimetres of mercury, with no significant effect on systemic blood pressure. 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: A single dose almost removed the pressure rise that low oxygen causes in the lung, without touching pressure elsewhere. organism: Human and 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

The events it takes part in

A mechanism often involves more than two components. These are the full events, with every participant and its role.

Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

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Open hypotheses

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

Hypoxic pulmonary vasoconstriction