Prostacyclin / prostaglandin I2

Where it participates (unsigned role)

1. 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.

   The vasodilatory prostaglandin reserve that supports renal blood flow under stress → Glomerular filtration rate measured by creatinine clearance source_derived_draftungraded
   Experimental context and source evidence

   evidence_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"}

   experimental_model

   Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data

   exposure

   Cyclooxygenase inhibition against a background of raised vasoconstrictor tone

   limitations

   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.

   nutrient_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. · Ibuprofen

   organism

   Rat, dog and human

   plain_language

   These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not.

   primary_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

   tissue_or_cell_type

   Renal cortex and glomeruli

   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) · lines 474–485

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data · source_derived_draft · unverified_draft

   ### ibu-a-reserve-not-a-baseline 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. Condition category: normal nutrient_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. plain_language: These prostaglandins are a reserve the kidney calls on under strain, which is why blocking them is harmless until it is not. organism: Rat, dog and human tissue_or_cell_type: Renal cortex and glomeruli experimental_model: Review of renal cortical prostaglandin physiology with dog bile duct ligation and human volunteer data limitations: 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. exposure: Cyclooxygenase inhibition against a background of raised vasoconstrictor tone evidence_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"} [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

   Complete structured claim and evidence

2. Ibuprofen but not celecoxib significantly inhibited thromboxane-dependent platelet aggregation induced ex vivo by arachidonic acid, 83% against 11.9%, and reduced serum thromboxane B2 by 95% and urinary 11-dehydro thromboxane B2 by 70%, while both ibuprofen and celecoxib suppressed an index of cyclooxygenase-2 activity to a comparable degree and both suppressed urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha, data suggesting that cyclooxygenase-2 is a major source of systemic prostacyclin biosynthesis in healthy humans.

   Ibuprofen → Systemic prostacyclin biosynthesis measured as urinary 2,3-dinor-6-keto-prostaglandin F1 alpha source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/ibuprofen-research/9874808.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4", "start_char": 0, "end_char": 1789, "text_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4"}

   experimental_model

   Volunteers given celecoxib at three doses or ibuprofen, with platelet, serum and urinary indices

   exposure

   800 milligrams ibuprofen against 100, 400 or 800 milligrams celecoxib

   limitations

   Measures both isoform-specific indices in the same people, which is what allows the prostacyclin source to be assigned. Acute dosing in healthy volunteers.

   nutrient_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. · Ibuprofen

   organism

   Human

   plain_language

   The enzyme these drugs are meant to spare the stomach by blocking is the one that makes the body’s main anticlotting prostaglandin.

   primary_references

   [ibu-p9874808] Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. (1999). https://pubmed.ncbi.nlm.nih.gov/9874808/ DOI: 10.1073/pnas.96.1.272

   tissue_or_cell_type

   Platelets and whole body

   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) · lines 526–537

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Volunteers given celecoxib at three doses or ibuprofen, with platelet, serum and urinary indices · source_derived_draft · unverified_draft

   ### ibu-cox2-makes-the-prostacyclin Ibuprofen but not celecoxib significantly inhibited thromboxane-dependent platelet aggregation induced ex vivo by arachidonic acid, 83% against 11.9%, and reduced serum thromboxane B2 by 95% and urinary 11-dehydro thromboxane B2 by 70%, while both ibuprofen and celecoxib suppressed an index of cyclooxygenase-2 activity to a comparable degree and both suppressed urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha, data suggesting that cyclooxygenase-2 is a major source of systemic prostacyclin biosynthesis in healthy humans. Condition category: normal nutrient_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. plain_language: The enzyme these drugs are meant to spare the stomach by blocking is the one that makes the body’s main anticlotting prostaglandin. organism: Human tissue_or_cell_type: Platelets and whole body experimental_model: Volunteers given celecoxib at three doses or ibuprofen, with platelet, serum and urinary indices limitations: Measures both isoform-specific indices in the same people, which is what allows the prostacyclin source to be assigned. Acute dosing in healthy volunteers. exposure: 800 milligrams ibuprofen against 100, 400 or 800 milligrams celecoxib evidence_span: {"source_cache": "artifacts/ibuprofen-research/9874808.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4", "start_char": 0, "end_char": 1789, "text_sha256": "a643d03df8bc925866696516e7040644634dca29b4f98d39df38ea9c9ab295f4"} [ibu-p9874808] Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. (1999). https://pubmed.ncbi.nlm.nih.gov/9874808/ DOI: 10.1073/pnas.96.1.272

   Complete structured claim and evidence

3. In 10 patients with chronic glomerular disease randomly assigned to one week of ibuprofen, urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 excretion fell by 80%, serum creatinine rose by 40% and creatinine and para-aminohippurate clearances fell by 28% and 35% respectively, with the reduction in both clearances inversely related to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2, while no functional changes were detected in five healthy women despite a similar suppression of renal prostacyclin synthesis, and one week of sulindac did not affect renal prostacyclin synthesis or renal function despite marked inhibition of extrarenal cyclooxygenase.

   Ibuprofen → Glomerular filtration rate measured by creatinine clearance source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/ibuprofen-research/6361565.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b", "start_char": 0, "end_char": 1550, "text_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b"}

   experimental_model

   Randomised one week treatment in 20 women with chronic glomerular disease and 5 healthy women

   exposure

   Ibuprofen for one week, against sulindac in a parallel group

   limitations

   The healthy comparison group is what makes this decisive: the same suppression of renal prostacyclin produced no functional change in them. Twenty patients, one week.

   nutrient_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. · Ibuprofen

   organism

   Human

   plain_language

   The same drop in kidney prostaglandins does nothing to a healthy kidney and takes a third of the function from a diseased one.

   primary_references

   [ibu-p6361565] Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. (1984). https://pubmed.ncbi.nlm.nih.gov/6361565/ DOI: 10.1056/nejm198402023100502

   tissue_or_cell_type

   Kidney

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   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) · lines 461–472

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised one week treatment in 20 women with chronic glomerular disease and 5 healthy women · source_derived_draft · unverified_draft

   ### ibu-kidney-depends-on-what-is-blocked In 10 patients with chronic glomerular disease randomly assigned to one week of ibuprofen, urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 excretion fell by 80%, serum creatinine rose by 40% and creatinine and para-aminohippurate clearances fell by 28% and 35% respectively, with the reduction in both clearances inversely related to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2, while no functional changes were detected in five healthy women despite a similar suppression of renal prostacyclin synthesis, and one week of sulindac did not affect renal prostacyclin synthesis or renal function despite marked inhibition of extrarenal cyclooxygenase. Condition category: biomarker_context nutrient_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. plain_language: The same drop in kidney prostaglandins does nothing to a healthy kidney and takes a third of the function from a diseased one. organism: Human tissue_or_cell_type: Kidney experimental_model: Randomised one week treatment in 20 women with chronic glomerular disease and 5 healthy women limitations: The healthy comparison group is what makes this decisive: the same suppression of renal prostacyclin produced no functional change in them. Twenty patients, one week. exposure: Ibuprofen for one week, against sulindac in a parallel group evidence_span: {"source_cache": "artifacts/ibuprofen-research/6361565.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b", "start_char": 0, "end_char": 1550, "text_sha256": "98ef6b906f4841d1488baebb3c03c7452c98c5266ae012dd2a0eb579661dc15b"} [ibu-p6361565] Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. (1984). https://pubmed.ncbi.nlm.nih.gov/6361565/ DOI: 10.1056/nejm198402023100502

   Complete structured claim and evidence

4. In rabbits lower doses of aspirin produced major inhibition of platelet aggregation and minor inhibition of prostacyclin synthesis while higher doses inhibited both, in humans a dose equivalent to approximately one quarter of one 300 milligram tablet consistently produced major inhibition of cyclooxygenase-dependent platelet aggregation in a pattern similar to that in rabbits where most prostacyclin synthetic capacity was not inhibited, and it took rabbit vasculature over 24 hours to return to control prostacyclin synthetic capacity after a single high dose.

   Aspirin / acetylsalicylic acid → Cyclooxygenase-dependent platelet aggregation source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/aspirin-research/6156337.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0d904fae5d8c006bd180213b6b2cbc88c87bb103b9c8b8872705330c349b074", "start_char": 0, "end_char": 1502, "text_sha256": "e0d904fae5d8c006bd180213b6b2cbc88c87bb103b9c8b8872705330c349b074"}

   experimental_model

   Human and rabbit platelet aggregation with rabbit aortic prostacyclin synthesis measured across aspirin doses

   exposure

   Graded oral aspirin doses, sampled three hours after dosing, with recovery followed over 24 hours in rabbits

   limitations

   Sets the dose at which the two tissues start to separate, but the vascular arm is rabbit aorta and the human arm measures aggregation rather than prostacyclin.

   nutrient_topic

   Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

   organism

   Human and rabbit

   plain_language

   About a quarter of a tablet stops the platelets while mostly leaving the vessel wall alone.

   primary_references

   [asa-p6156337] Effect of oral aspirin dose on platelet aggregation and vascular prostacyclin (PGI2) synthesis in humans and rabbits. (1980). https://pubmed.ncbi.nlm.nih.gov/6156337/ DOI: 10.1097/00005344-198007000-00006

   tissue_or_cell_type

   Platelets and aorta

   Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 390–401

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and rabbit platelet aggregation with rabbit aortic prostacyclin synthesis measured across aspirin doses · source_derived_draft · unverified_draft

   ### asa-a-quarter-tablet In rabbits lower doses of aspirin produced major inhibition of platelet aggregation and minor inhibition of prostacyclin synthesis while higher doses inhibited both, in humans a dose equivalent to approximately one quarter of one 300 milligram tablet consistently produced major inhibition of cyclooxygenase-dependent platelet aggregation in a pattern similar to that in rabbits where most prostacyclin synthetic capacity was not inhibited, and it took rabbit vasculature over 24 hours to return to control prostacyclin synthetic capacity after a single high dose. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: About a quarter of a tablet stops the platelets while mostly leaving the vessel wall alone. organism: Human and rabbit tissue_or_cell_type: Platelets and aorta experimental_model: Human and rabbit platelet aggregation with rabbit aortic prostacyclin synthesis measured across aspirin doses limitations: Sets the dose at which the two tissues start to separate, but the vascular arm is rabbit aorta and the human arm measures aggregation rather than prostacyclin. exposure: Graded oral aspirin doses, sampled three hours after dosing, with recovery followed over 24 hours in rabbits evidence_span: {"source_cache": "artifacts/aspirin-research/6156337.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e0d904fae5d8c006bd180213b6b2cbc88c87bb103b9c8b8872705330c349b074", "start_char": 0, "end_char": 1502, "text_sha256": "e0d904fae5d8c006bd180213b6b2cbc88c87bb103b9c8b8872705330c349b074"} [asa-p6156337] Effect of oral aspirin dose on platelet aggregation and vascular prostacyclin (PGI2) synthesis in humans and rabbits. (1980). https://pubmed.ncbi.nlm.nih.gov/6156337/ DOI: 10.1097/00005344-198007000-00006

   Complete structured claim and evidence

5. Two hours after 150 or 300 milligrams of aspirin, 81 to 100% inhibition of vein-wall prostacyclin synthesis was demonstrated with 86% inhibition still evident in one subject at eight hours, while platelet thromboxane B2 production was completely inhibited for more than 24 hours, leading to the conclusion that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses, and that the prolonged bleeding time after aspirin is not a consequence of selective inhibition of platelet thromboxane production.

   Aspirin / acetylsalicylic acid → Prostacyclin synthesis by the vessel wall source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/aspirin-research/7003384.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38", "start_char": 0, "end_char": 1148, "text_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38"}

   experimental_model

   Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites

   exposure

   150 or 300 milligrams of oral aspirin

   limitations

   Five subjects, and the vein segments are surgically obtained rather than sampled in situ. Its conclusion is the opposite of the low-dose study in this collection and the doses differ tenfold.

   nutrient_topic

   Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid

   organism

   Human

   plain_language

   At ordinary tablet doses the vessel wall is hit about as hard as the platelet.

   primary_references

   [asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203

   tissue_or_cell_type

   Vein wall and platelets

   Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 377–388

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites · source_derived_draft · unverified_draft

   ### asa-no-selectivity-at-higher-dose Two hours after 150 or 300 milligrams of aspirin, 81 to 100% inhibition of vein-wall prostacyclin synthesis was demonstrated with 86% inhibition still evident in one subject at eight hours, while platelet thromboxane B2 production was completely inhibited for more than 24 hours, leading to the conclusion that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses, and that the prolonged bleeding time after aspirin is not a consequence of selective inhibition of platelet thromboxane production. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: At ordinary tablet doses the vessel wall is hit about as hard as the platelet. organism: Human tissue_or_cell_type: Vein wall and platelets experimental_model: Vein segments and platelets sampled from five subjects before and after aspirin, with radioimmunoassay of stable metabolites limitations: Five subjects, and the vein segments are surgically obtained rather than sampled in situ. Its conclusion is the opposite of the low-dose study in this collection and the doses differ tenfold. exposure: 150 or 300 milligrams of oral aspirin evidence_span: {"source_cache": "artifacts/aspirin-research/7003384.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38", "start_char": 0, "end_char": 1148, "text_sha256": "b54b61e084b6ec232b9c86ef5de713b0d5a57def2525eb6d3d50e5d7768e5c38"} [asa-p7003384] Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. (1981). https://pubmed.ncbi.nlm.nih.gov/7003384/ DOI: 10.1056/nejm198101083040203

   Complete structured claim and evidence