{"id":"ace32374-a1d0-59ab-9b04-24f9fa823797","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-a-reserve-not-a-baseline","predicate":"maintains","statement":"Vasodilatory renal prostaglandins are relatively unimportant under normal circumstances but play a modulatory role after ischaemia or in the presence of increased concentrations of vasoconstrictor substances such as angiotensin II, vasopressin or norepinephrine, indomethacin potentiates the renal actions of angiotensin II in vivo particularly the reduction of renal blood flow and filtration rate, and in dogs after chronic bile duct ligation cyclooxygenase inhibition by indomethacin, ibuprofen, naproxen or sulindac sulfide produced a comparable 50% decrease in both renal blood flow and filtration rate.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"093a1308-d97b-5e06-9bfb-b86871f454b3","mechanism_event_label":"These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not.","subject":{"id":"9afed0d4-ed1c-5f57-ad14-262e92a5cb61","slug":"renal-vasodilatory-reserve","display_name":"The vasodilatory prostaglandin reserve that supports renal blood flow under stress","entity_type_key":"cellular_process"},"object":{"id":"f40f8e7f-25f1-530d-bc4b-08374630e3c0","slug":"glomerular-filtration-rate","display_name":"Glomerular filtration rate measured by creatinine clearance","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"093a1308-d97b-5e06-9bfb-b86871f454b3","stable_key":"3238e4f0-8d45-5c72-8624-6e9a8b20527c:ibu-a-reserve-not-a-baseline-event","event_type":"observed_intervention","label":"These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not.","description":"Vasodilatory renal prostaglandins are relatively unimportant under normal circumstances but play a modulatory role after ischaemia or in the presence of increased concentrations of vasoconstrictor substances such as angiotensin II, vasopressin or norepinephrine, indomethacin potentiates the renal actions of angiotensin II in vivo particularly the reduction of renal blood flow and filtration rate, and in dogs after chronic bile duct ligation cyclooxygenase inhibition by indomethacin, ibuprofen, naproxen or sulindac sulfide produced a comparable 50% decrease in both renal blood flow and filtration rate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"67549473-d3dd-5cc2-b24d-b7f254ff770b","slug":"angiotensin-ii","display_name":"Angiotensin II","entity_type_key":"peptide"},"role":"opposed_constrictor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"10d57fac-7c12-5954-9317-d5818678e670","slug":"vasopressin","display_name":"Arginine vasopressin / antidiuretic hormone","entity_type_key":"small_molecule"},"role":"opposed_constrictor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5733d7d1-6259-588f-a4a9-4d0dc0133735","slug":"prostaglandin-e2","display_name":"Prostaglandin E2","entity_type_key":"small_molecule"},"role":"protective_mediator","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"25063538-7b79-5cd4-9839-511490482e03","slug":"prostacyclin","display_name":"Prostacyclin / prostaglandin I2","entity_type_key":"small_molecule"},"role":"protective_mediator","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"900e4922-ec36-5b77-bb7a-981c8a5c41a6","slug":"renal-plasma-flow","display_name":"Renal plasma flow measured by para-aminohippurate clearance","entity_type_key":"cellular_process"},"role":"supported_measure","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"9afed0d4-ed1c-5f57-ad14-262e92a5cb61","slug":"renal-vasodilatory-reserve","display_name":"The vasodilatory prostaglandin reserve that supports renal blood flow under stress","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"f40f8e7f-25f1-530d-bc4b-08374630e3c0","slug":"glomerular-filtration-rate","display_name":"Glomerular filtration rate measured by creatinine clearance","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/ibuprofen-research/6595999.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2\", \"start_char\": 0, \"end_char\": 2422, \"text_sha256\": \"cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Cyclooxygenase inhibition against a background of raised vasoconstrictor tone","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A review assembling several models rather than one experiment. It states the conditional nature of the renal prostaglandin role, which is the point recorded here.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ibuprofen","display_name":"Ibuprofen","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Rat, dog and human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ibu-p6595999] Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. (1984). https://pubmed.ncbi.nlm.nih.gov/6595999/ DOI: 10.1007/978-3-642-69132-4_56","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Renal cortex and glomeruli","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e866d124-f046-5471-8536-ae8c0f926ec3","evidence_kind":"source_excerpt","locator":"Lines 474-485","start_line":474,"end_line":485,"excerpt":"### ibu-a-reserve-not-a-baseline\nVasodilatory renal prostaglandins are relatively unimportant under normal circumstances but play a modulatory role after ischaemia or in the presence of increased concentrations of vasoconstrictor substances such as angiotensin II, vasopressin or norepinephrine, indomethacin potentiates the renal actions of angiotensin II in vivo particularly the reduction of renal blood flow and filtration rate, and in dogs after chronic bile duct ligation cyclooxygenase inhibition by indomethacin, ibuprofen, naproxen or sulindac sulfide produced a comparable 50% decrease in both renal blood flow and filtration rate.\nCondition category: normal\nnutrient_topic: Ibuprofen research collection; topical membership is not evidence of a direct clinical effect, and the racemate is recorded separately from each of its two enantiomers.\nplain_language: These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not.\norganism: Rat, dog and human\ntissue_or_cell_type: Renal cortex and glomeruli\nexperimental_model: Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data\nlimitations: A review assembling several models rather than one experiment. It states the conditional nature of the renal prostaglandin role, which is the point recorded here.\nexposure: Cyclooxygenase inhibition against a background of raised vasoconstrictor tone\nevidence_span: {\"source_cache\": \"artifacts/ibuprofen-research/6595999.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2\", \"start_char\": 0, \"end_char\": 2422, \"text_sha256\": \"cf73667739f04e5edcaf0e75c1f413cbda7abbfe84b8701b1aeaa347b67809c2\"}\n[ibu-p6595999] Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. (1984). https://pubmed.ncbi.nlm.nih.gov/6595999/ DOI: 10.1007/978-3-642-69132-4_56","model_system":"Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ibu-p6595999] Mechanisms of the nephrotoxicity of non-steroidal anti-inflammatory drugs. (1984). https://pubmed.ncbi.nlm.nih.gov/6595999/ DOI: 10.1007/978-3-642-69132-4_56","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"31c4939d-f520-55c0-973b-224743caf245","stable_key":"import-3238e4f0-8d45-5c72-8624-6e9a8b20527c","title":"Ibuprofen: the enantiomer that works, the one that was called inactive, the one-way chemistry that turns one into the other, and the targets that are not cyclooxygenase (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":"cc2b388178f97f5906b66ecbe441fc5c86d51fd645947c5260fb0b4bdb4bcd21","revision_id":"0b4e5c65-05d3-5430-a4cd-8d6a03647dcb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}