{"id":"9bb83d2a-2574-54ce-826d-fc87d1b046eb","stable_key":"252872b9-233f-5692-b72b-c8930ba0cfb7:sil-abolishes-the-hypoxic-rise","predicate":"reduces","statement":"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.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"4a1ce4ac-31cc-528b-9234-d21be53f443c","mechanism_event_label":"A single dose almost removed the pressure rise that low oxygen causes in the lung, without touching pressure elsewhere.","subject":{"id":"fe62cf8d-5f89-5e19-bc36-03ad3c9063b7","slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"},"object":{"id":"47dc8e5a-5f3b-55d9-abbd-9b7f8b3e122c","slug":"pulmonary-artery-pressure","display_name":"Mean or systolic pulmonary artery pressure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4a1ce4ac-31cc-528b-9234-d21be53f443c","stable_key":"252872b9-233f-5692-b72b-c8930ba0cfb7:sil-abolishes-the-hypoxic-rise-event","event_type":"observed_intervention","label":"A single dose almost removed the pressure rise that low oxygen causes in the lung, without touching pressure elsewhere.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"4c965136-118d-59f3-8c2f-364356772009","slug":"hypoxic-pulmonary-vasoconstriction","display_name":"Hypoxic pulmonary vasoconstriction","entity_type_key":"cellular_process"},"role":"suppressed_response","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"736a4c55-284d-5361-bf7a-459544e16af1","slug":"systemic-blood-pressure","display_name":"Systemic arterial blood pressure","entity_type_key":"cellular_process"},"role":"spared_measure","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fe62cf8d-5f89-5e19-bc36-03ad3c9063b7","slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"47dc8e5a-5f3b-55d9-abbd-9b7f8b3e122c","slug":"pulmonary-artery-pressure","display_name":"Mean or systolic pulmonary artery pressure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":{"slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human and mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A single dose almost removed the pressure rise that low oxygen causes in the lung, without touching pressure elsewhere.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sil-p11468204] Sildenafil inhibits hypoxia-induced pulmonary hypertension. (2001). https://pubmed.ncbi.nlm.nih.gov/11468204/ DOI: 10.1161/hc2901.093117","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Pulmonary circulation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"05f86f20-da74-5251-8453-4b7f19a3cc3b","evidence_kind":"source_excerpt","locator":"Lines 522-533","start_line":522,"end_line":533,"excerpt":"### sil-abolishes-the-hypoxic-rise\nIn 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.\nCondition category: normal\nnutrient_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.\nplain_language: A single dose almost removed the pressure rise that low oxygen causes in the lung, without touching pressure elsewhere.\norganism: Human and mouse\ntissue_or_cell_type: Pulmonary circulation\nexperimental_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\nlimitations: 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.\nexposure: 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\nevidence_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\"}\n[sil-p11468204] Sildenafil inhibits hypoxia-induced pulmonary hypertension. (2001). https://pubmed.ncbi.nlm.nih.gov/11468204/ DOI: 10.1161/hc2901.093117","model_system":"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","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [sil-p11468204] Sildenafil inhibits hypoxia-induced pulmonary hypertension. (2001). https://pubmed.ncbi.nlm.nih.gov/11468204/ DOI: 10.1161/hc2901.093117","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c6c2a590-1f8f-5fac-b2c7-3aae0440b9fd","stable_key":"import-252872b9-233f-5692-b72b-c8930ba0cfb7","title":"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)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"bc81793d20d20d2eaad9cb530b70695d8d8778a3d7136e24715ac3369b939953","revision_id":"301732e1-2446-5b67-b3bd-580164b85b05","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}