Mean or systolic pulmonary artery pressure

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

evidence_span

{"source_cache": "artifacts/sildenafil-research/12760589.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5", "start_char": 0, "end_char": 2507, "text_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5"}

experimental_model

Randomised double-blind placebo-controlled crossover trial in ten consecutive patients poorly controlled on conventional therapy

exposure

Sildenafil 25 milligrams every eight hours or matching placebo for two weeks each with a two-week run-in between

limitations

Ten patients of mixed aetiology, with pulmonary artery pressure estimated by echo Doppler rather than catheter, and a two-week exposure.

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

plain_language

Two weeks of tablets let these patients walk nearly a hundred metres further and dropped the pressure in the lung.

primary_references

[sil-p12760589] The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12760589/

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 574–585

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised double-blind placebo-controlled crossover trial in ten consecutive patients poorly controlled on conventional therapy · source_derived_draft · unverified_draft

### sil-improves-walking-and-pressure In ten patients with pulmonary hypertension either primary or related to previous left-to-right shunts, thromboembolism or interstitial lung disease and poorly controlled on conventional therapy, sildenafil 25 milligrams eight hourly for two weeks was associated compared with placebo with improved exercise tolerance on the six-minute walk test at 266.67 against 170 metres, a decrease in modified Borg dyspnea score from 5.11 to 3.56, a decrease in Doppler-estimated pulmonary artery systolic pressure from 75.33 to 55.33 millimetres of mercury, and improvement in New York Heart Association class in two patients, with no significant changes in heart rate or 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: Two weeks of tablets let these patients walk nearly a hundred metres further and dropped the pressure in the lung. organism: Human tissue_or_cell_type: Pulmonary circulation experimental_model: Randomised double-blind placebo-controlled crossover trial in ten consecutive patients poorly controlled on conventional therapy limitations: Ten patients of mixed aetiology, with pulmonary artery pressure estimated by echo Doppler rather than catheter, and a two-week exposure. exposure: Sildenafil 25 milligrams every eight hours or matching placebo for two weeks each with a two-week run-in between evidence_span: {"source_cache": "artifacts/sildenafil-research/12760589.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5", "start_char": 0, "end_char": 2507, "text_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5"} [sil-p12760589] The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12760589/

evidence_span

{"source_cache": "artifacts/sildenafil-research/11351772.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73a1ab2fa66fb9a6155ab7ccae7f405568ffdee07d4a09d61dc106e00c442711", "start_char": 0, "end_char": 1020, "text_sha256": "73a1ab2fa66fb9a6155ab7ccae7f405568ffdee07d4a09d61dc106e00c442711"}

experimental_model

Review of the coronary vascular profile assembled from haemodynamic studies and retrospective analysis of the clinical trial programme

exposure

Sildenafil at therapeutic doses in men with coronary heart disease not taking nitrates

limitations

A review rather than a new study, and the cardiac risk analyses are retrospective. It measures coronary flow in the intact circulation, where the organ bath records cannot.

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

plain_language

In the living coronary circulation it did not change resting flow, though it improved the reserve the vessels could call on.

primary_references

[sil-p11351772] Phosphodiesterase 5 inhibition: effects on the coronary vasculature. (2001). https://pubmed.ncbi.nlm.nih.gov/11351772/ DOI: 10.1111/j.1742-1241.2001.tb11011.x

tissue_or_cell_type

Coronary 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 379–390

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of the coronary vascular profile assembled from haemodynamic studies and retrospective analysis of the clinical trial programme · source_derived_draft · unverified_draft

### sil-no-change-in-coronary-flow In haemodynamic studies sildenafil produced small decreases in systemic and pulmonary blood pressure but caused no adverse cardiovascular effects in specific populations of men with coronary heart disease, and it caused no significant changes in coronary blood flow but had a positive effect on coronary flow reserve in men with severe coronary artery disease, suggesting that PDE5 may play an important role in the regulation of coronary blood flow in the healthy and diseased heart, while in retrospective analyses of extensive clinical trials treatment was not associated with any increase in cardiac risk in patients not receiving organic nitrates or nitrate donor drugs. 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: In the living coronary circulation it did not change resting flow, though it improved the reserve the vessels could call on. organism: Human tissue_or_cell_type: Coronary circulation experimental_model: Review of the coronary vascular profile assembled from haemodynamic studies and retrospective analysis of the clinical trial programme limitations: A review rather than a new study, and the cardiac risk analyses are retrospective. It measures coronary flow in the intact circulation, where the organ bath records cannot. exposure: Sildenafil at therapeutic doses in men with coronary heart disease not taking nitrates evidence_span: {"source_cache": "artifacts/sildenafil-research/11351772.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73a1ab2fa66fb9a6155ab7ccae7f405568ffdee07d4a09d61dc106e00c442711", "start_char": 0, "end_char": 1020, "text_sha256": "73a1ab2fa66fb9a6155ab7ccae7f405568ffdee07d4a09d61dc106e00c442711"} [sil-p11351772] Phosphodiesterase 5 inhibition: effects on the coronary vasculature. (2001). https://pubmed.ncbi.nlm.nih.gov/11351772/ DOI: 10.1111/j.1742-1241.2001.tb11011.x

evidence_span

{"source_cache": "artifacts/sildenafil-research/15289213.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136", "start_char": 0, "end_char": 2481, "text_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136"}

experimental_model

Randomised double-blind placebo-controlled crossover study in fourteen mountaineers at low altitude under hypoxic gas and at Mount Everest base camp

exposure

Oral sildenafil 50 milligrams, with systolic pulmonary artery pressure, cardiac output and arterial oxygen saturation at rest and at maximum exercise

limitations

A crossover design carried out in two settings including genuine altitude. Fourteen participants, and the study did not examine normoxic exercise tolerance.

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

plain_language

By lowering the pressure the lung raises against low oxygen, it let people work substantially harder.

primary_references

[sil-p15289213] Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. (2004). https://pubmed.ncbi.nlm.nih.gov/15289213/ DOI: 10.7326/0003-4819-141-3-200408030-00005

tissue_or_cell_type

Pulmonary circulation and exercise capacity

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 587–598

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised double-blind placebo-controlled crossover study in fourteen mountaineers at low altitude under hypoxic gas and at Mount Everest base camp · source_derived_draft · unverified_draft

### sil-raises-exercise-capacity-in-hypoxia At low altitude under 10 percent inspired oxygen sildenafil 50 milligrams significantly increased arterial oxygen saturation during exercise, reduced systolic pulmonary artery pressure at rest and during exercise, and increased maximum workload from 130.6 to 172.5 watts and maximum cardiac output, while at Mount Everest base camp it had no effect on arterial oxygen saturation but still reduced systolic pulmonary artery pressure at rest and during exercise and increased maximum workload and cardiac output, exacerbating existing headache in two participants. 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: By lowering the pressure the lung raises against low oxygen, it let people work substantially harder. organism: Human tissue_or_cell_type: Pulmonary circulation and exercise capacity experimental_model: Randomised double-blind placebo-controlled crossover study in fourteen mountaineers at low altitude under hypoxic gas and at Mount Everest base camp limitations: A crossover design carried out in two settings including genuine altitude. Fourteen participants, and the study did not examine normoxic exercise tolerance. exposure: Oral sildenafil 50 milligrams, with systolic pulmonary artery pressure, cardiac output and arterial oxygen saturation at rest and at maximum exercise evidence_span: {"source_cache": "artifacts/sildenafil-research/15289213.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136", "start_char": 0, "end_char": 2481, "text_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136"} [sil-p15289213] Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. (2004). https://pubmed.ncbi.nlm.nih.gov/15289213/ DOI: 10.7326/0003-4819-141-3-200408030-00005

evidence_span

{"source_cache": "artifacts/sildenafil-research/12796132.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122", "start_char": 0, "end_char": 1616, "text_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122"}

experimental_model

Continuous telemetric pulmonary artery pressure measurement with immunolocalisation and morphometry in rats exposed to hypoxia for up to 42 days

exposure

Sildenafil 25 or 75 milligrams per kilogram per day started before hypoxia, or started after 14 days of established pulmonary hypertension

limitations

The delayed-treatment arm is what distinguishes prevention from reversal. A rat hypoxia model, and the reversal of muscularisation is partial.

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

Rat

plain_language

Started after the damage was already there, it still pushed the pressure down and partly undid the thickening.

primary_references

[sil-p12796132] Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12796132/ DOI: 10.1161/01.cir.0000074226.20466.b1

tissue_or_cell_type

Pulmonary vascular tree

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 561–572

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Continuous telemetric pulmonary artery pressure measurement with immunolocalisation and morphometry in rats exposed to hypoxia for up to 42 days · source_derived_draft · unverified_draft

### sil-reverses-established-remodelling PDE5 immunoreactivity was localized to smooth muscle cells in the medial layer of pulmonary arteries and veins in the normal rat lung and in distal muscularized arteries under 25 micrometres in diameter after hypoxia-induced pulmonary hypertension, sildenafil at 25 or 75 milligrams per kilogram per day given before hypoxia produced marked dose-dependent inhibition in the rise of pulmonary artery pressure of 60 to 90% and a 28.4% reduction in vascular muscularization, and when begun after 14 days of hypoxia it significantly reduced pulmonary artery pressure by 30% and partially reversed pulmonary artery muscularization by 39.9%. 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: Started after the damage was already there, it still pushed the pressure down and partly undid the thickening. organism: Rat tissue_or_cell_type: Pulmonary vascular tree experimental_model: Continuous telemetric pulmonary artery pressure measurement with immunolocalisation and morphometry in rats exposed to hypoxia for up to 42 days limitations: The delayed-treatment arm is what distinguishes prevention from reversal. A rat hypoxia model, and the reversal of muscularisation is partial. exposure: Sildenafil 25 or 75 milligrams per kilogram per day started before hypoxia, or started after 14 days of established pulmonary hypertension evidence_span: {"source_cache": "artifacts/sildenafil-research/12796132.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122", "start_char": 0, "end_char": 1616, "text_sha256": "61d9020b6275a7c57fcee753c74b06c334ad034286eeaccdcbdf12e49b472122"} [sil-p12796132] Phosphodiesterase type 5 as a target for the treatment of hypoxia-induced pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12796132/ DOI: 10.1161/01.cir.0000074226.20466.b1