{"id":"16a2ed73-9979-5da2-8809-cf5781f4798e","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-pig-combination-pvr","predicate":"reduced","statement":"Combined citrulline and BH4 improved pulmonary vascular resistance more than either alone in hypoxic piglets.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"0b0fa7c7-2320-5efc-96d6-77f58009a2d0","mechanism_event_label":"Both substrate supply and cofactor support mattered in this animal model.","subject":{"id":"aa0a5df7-e14c-5220-8705-b59d6e7e943c","slug":"citrulline-bh4-combination","display_name":"L-Citrulline plus tetrahydrobiopterin, study-specific combination","entity_type_key":"chemical_species"},"object":{"id":"1281917e-51e4-520b-b8d9-5f01d2a81452","slug":"pulmonary-vascular-resistance","display_name":"Pulmonary vascular resistance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0b0fa7c7-2320-5efc-96d6-77f58009a2d0","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-pig-combination-pvr-event","event_type":"biochemical_relationship","label":"Both substrate supply and cofactor support mattered in this animal model.","description":"Combined citrulline and BH4 improved pulmonary vascular resistance more than either alone in hypoxic piglets.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f53c7bfb-3b91-56fe-bebd-28623cfe13a0","slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"},"role":"combination_component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1c231b90-c106-507a-8766-870ecb40e368","slug":"tetrahydrobiopterin","display_name":"Tetrahydrobiopterin / BH4","entity_type_key":"small_molecule"},"role":"combination_component","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d820ba20-1252-5e94-a0f2-27bf6f9cf8f5","slug":"porcine-nos3","display_name":"Pig endothelial nitric oxide synthase / NOS3","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"aa0a5df7-e14c-5220-8705-b59d6e7e943c","slug":"citrulline-bh4-combination","display_name":"L-Citrulline plus tetrahydrobiopterin, study-specific combination","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"1281917e-51e4-520b-b8d9-5f01d2a81452","slug":"pulmonary-vascular-resistance","display_name":"Pulmonary vascular resistance","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Controlled neonatal hypoxia and combination-treatment experiment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"L-citrulline, sapropterin, or both during days 3-10 of hypoxia","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Citrulline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Newborn pig","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Both substrate supply and cofactor support mattered in this animal model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Pulmonary arteries and hemodynamics","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0badf8e5-1807-5505-b0d9-46f3ef94860e","evidence_kind":"source_excerpt","locator":"Lines 814-825","start_line":814,"end_line":825,"excerpt":"### citrulline-pig-combination-pvr\nCombined citrulline and BH4 improved pulmonary vascular resistance more than either alone in hypoxic piglets.\nCondition category: normal\nnutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Both substrate supply and cofactor support mattered in this animal model.\norganism: Newborn pig\ntissue_or_cell_type: Pulmonary arteries and hemodynamics\nexperimental_model: Controlled neonatal hypoxia and combination-treatment experiment\nlimitations: Animal combination evidence; does not establish neonatal clinical dosing or treatment benefit in humans.\nexposure: L-citrulline, sapropterin, or both during days 3-10 of hypoxia\nevidence_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\"}\n[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","model_system":"Controlled neonatal hypoxia and combination-treatment experiment","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"112fd375-aa2a-59d2-8afd-6b2849bb79ee","stable_key":"import-a9828b14-fbd7-57bf-9e01-0d52d1b42a1f","title":"Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17)","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":"3720442dbabc28cacefd2145c7c97bfb937df26dca8527fde219ecd3735ed558","revision_id":"41ac8493-b004-59d7-99b3-8a3ca7163d3a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}