Systemic arterial blood pressure

Where it participates (unsigned role)

1. 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.

   Sildenafil → Mean or systolic pulmonary artery pressure source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence

2. In thirteen patients with severe pulmonary hypertension the decrease in pulmonary vascular resistance was similar with inhaled nitric oxide at 19% and sildenafil at 27% while the combination was more effective than inhaled nitric oxide alone at 32%, sildenafil and the combination increased cardiac index by 17% whereas inhaled nitric oxide did not, inhaled nitric oxide increased whereas sildenafil tended to decrease pulmonary capillary wedge pressure, systemic arterial pressure was similar among groups and did not decrease, and cyclic GMP rose similarly with each agent while the combination raised it synergistically.

   Sildenafil → Pulmonary vascular resistance source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/sildenafil-research/12021227.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0", "start_char": 0, "end_char": 1828, "text_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0"}

   experimental_model

   Acute haemodynamic study in thirteen consecutive patients referred for transplantation assessment or therapy guidance

   exposure

   Inhaled nitric oxide at 80 parts per million, oral sildenafil 75 milligrams, and the combination, with serum cyclic GMP measured

   limitations

   Compares the drug directly against the reference selective pulmonary vasodilator in the same patients and measures the messenger. Thirteen patients and a single dose.

   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

   An oral tablet matched inhaled nitric oxide as a selective lung vasodilator and, unlike it, raised cardiac output.

   primary_references

   [sil-p12021227] Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. (2002). https://pubmed.ncbi.nlm.nih.gov/12021227/ DOI: 10.1161/01.cir.0000016641.12984.dc

   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 535–546

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute haemodynamic study in thirteen consecutive patients referred for transplantation assessment or therapy guidance · source_derived_draft · unverified_draft

   ### sil-as-selective-as-inhaled-no In thirteen patients with severe pulmonary hypertension the decrease in pulmonary vascular resistance was similar with inhaled nitric oxide at 19% and sildenafil at 27% while the combination was more effective than inhaled nitric oxide alone at 32%, sildenafil and the combination increased cardiac index by 17% whereas inhaled nitric oxide did not, inhaled nitric oxide increased whereas sildenafil tended to decrease pulmonary capillary wedge pressure, systemic arterial pressure was similar among groups and did not decrease, and cyclic GMP rose similarly with each agent while the combination raised it synergistically. 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: An oral tablet matched inhaled nitric oxide as a selective lung vasodilator and, unlike it, raised cardiac output. organism: Human tissue_or_cell_type: Pulmonary circulation experimental_model: Acute haemodynamic study in thirteen consecutive patients referred for transplantation assessment or therapy guidance limitations: Compares the drug directly against the reference selective pulmonary vasodilator in the same patients and measures the messenger. Thirteen patients and a single dose. exposure: Inhaled nitric oxide at 80 parts per million, oral sildenafil 75 milligrams, and the combination, with serum cyclic GMP measured evidence_span: {"source_cache": "artifacts/sildenafil-research/12021227.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0", "start_char": 0, "end_char": 1828, "text_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0"} [sil-p12021227] Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. (2002). https://pubmed.ncbi.nlm.nih.gov/12021227/ DOI: 10.1161/01.cir.0000016641.12984.dc

   Complete structured claim and evidence

3. In men with hypertension taking 5 or 10 milligrams daily of amlodipine, whose mechanism of action does not involve the cyclic GMP pathway, coadministration of a single 100 milligram dose of sildenafil did not significantly affect amlodipine pharmacokinetics and produced additive but not synergistic reductions in blood pressure, the differences in mean maximum change from baseline being 8 and 7 millimetres of mercury and comparable to the decrease reported for healthy men taking sildenafil alone.

   Amlodipine → Potentiation of the hypotensive effect of an organic nitrate source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/sildenafil-research/10078539.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654", "start_char": 0, "end_char": 3999, "text_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654"}

   experimental_model

   Double-blind placebo-controlled crossover studies of nitrate and calcium antagonist coadministration in healthy men and men with hypertension

   exposure

   Sildenafil 25 milligrams three times daily with stepwise intravenous and sublingual glyceryl trinitrate, and a single 100 milligram dose with amlodipine

   limitations

   The design that establishes the contraindication, and the amlodipine arm is the control that shows it is specific to the shared pathway rather than additive antihypertensive effect.

   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

   A blood pressure drug working by another route simply adds; only the ones sharing this pathway multiply.

   primary_references

   [sil-p10078539] Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. (1999). https://pubmed.ncbi.nlm.nih.gov/10078539/ DOI: 10.1016/s0002-9149(99)00044-2

   tissue_or_cell_type

   Systemic 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 418–429

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled crossover studies of nitrate and calcium antagonist coadministration in healthy men and men with hypertension · source_derived_draft · unverified_draft

   ### sil-calcium-antagonist-only-additive In men with hypertension taking 5 or 10 milligrams daily of amlodipine, whose mechanism of action does not involve the cyclic GMP pathway, coadministration of a single 100 milligram dose of sildenafil did not significantly affect amlodipine pharmacokinetics and produced additive but not synergistic reductions in blood pressure, the differences in mean maximum change from baseline being 8 and 7 millimetres of mercury and comparable to the decrease reported for healthy men taking sildenafil alone. 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 blood pressure drug working by another route simply adds; only the ones sharing this pathway multiply. organism: Human tissue_or_cell_type: Systemic circulation experimental_model: Double-blind placebo-controlled crossover studies of nitrate and calcium antagonist coadministration in healthy men and men with hypertension limitations: The design that establishes the contraindication, and the amlodipine arm is the control that shows it is specific to the shared pathway rather than additive antihypertensive effect. exposure: Sildenafil 25 milligrams three times daily with stepwise intravenous and sublingual glyceryl trinitrate, and a single 100 milligram dose with amlodipine evidence_span: {"source_cache": "artifacts/sildenafil-research/10078539.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654", "start_char": 0, "end_char": 3999, "text_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654"} [sil-p10078539] Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. (1999). https://pubmed.ncbi.nlm.nih.gov/10078539/ DOI: 10.1016/s0002-9149(99)00044-2

   Complete structured claim and evidence

4. 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.

   Sildenafil → Six-minute walk distance source_derived_draftungraded
   Experimental context and source evidence

   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/

   Complete structured claim and evidence

5. 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.

   Sildenafil → Coronary blood flow and coronary flow reserve source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence

6. The effects of pelvic nerve stimulation on intracavernosal pressure and penile blood flow were blocked by N-omega-nitro-L-arginine in a dose-related manner confirming the role of nitric oxide, and intravenous sildenafil at 1 to 100 micrograms per kilogram had no direct effect on intracavernosal pressure but potentiated the increase induced by nerve stimulation at plasma concentrations consistent with its relaxation effect on isolated human cavernosal tissue and its inhibition of the enzyme in vitro, with no significant effect on blood pressure or heart rate.

   Sildenafil → Intracavernosal pressure source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/sildenafil-research/9628657.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71870b989514f322eb55b17364921cc67de92b3deef59bdf75e2c35db6a97ff7", "start_char": 0, "end_char": 1781, "text_sha256": "71870b989514f322eb55b17364921cc67de92b3deef59bdf75e2c35db6a97ff7"}

   experimental_model

   Pentobarbital-anaesthetised dogs with pelvic nerve stimulation and nitric oxide synthase inhibition

   exposure

   Intravenous sildenafil 1 to 100 micrograms per kilogram, with N-omega-nitro-L-arginine

   limitations

   An in vivo test of the amplifier principle with the nitric oxide synthase inhibitor as the control. Anaesthetised animals.

   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

   Dog

   plain_language

   In the living animal it raised nothing by itself and roughly doubled what the nerve was already doing.

   primary_references

   [sil-p9628657] Effect of the selective phosphodiesterase type 5 inhibitor sildenafil on erectile dysfunction in the anesthetized dog. (1998). https://pubmed.ncbi.nlm.nih.gov/9628657/ DOI: 10.1016/s0022-5347(01)63097-0

   tissue_or_cell_type

   Corpus cavernosum and systemic circulation

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   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 301–312

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pentobarbital-anaesthetised dogs with pelvic nerve stimulation and nitric oxide synthase inhibition · source_derived_draft · unverified_draft

   ### sil-potentiates-only-the-nerve-signal The effects of pelvic nerve stimulation on intracavernosal pressure and penile blood flow were blocked by N-omega-nitro-L-arginine in a dose-related manner confirming the role of nitric oxide, and intravenous sildenafil at 1 to 100 micrograms per kilogram had no direct effect on intracavernosal pressure but potentiated the increase induced by nerve stimulation at plasma concentrations consistent with its relaxation effect on isolated human cavernosal tissue and its inhibition of the enzyme in vitro, with no significant effect on blood pressure or heart rate. Condition category: biomarker_context 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 animal it raised nothing by itself and roughly doubled what the nerve was already doing. organism: Dog tissue_or_cell_type: Corpus cavernosum and systemic circulation experimental_model: Pentobarbital-anaesthetised dogs with pelvic nerve stimulation and nitric oxide synthase inhibition limitations: An in vivo test of the amplifier principle with the nitric oxide synthase inhibitor as the control. Anaesthetised animals. exposure: Intravenous sildenafil 1 to 100 micrograms per kilogram, with N-omega-nitro-L-arginine evidence_span: {"source_cache": "artifacts/sildenafil-research/9628657.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71870b989514f322eb55b17364921cc67de92b3deef59bdf75e2c35db6a97ff7", "start_char": 0, "end_char": 1781, "text_sha256": "71870b989514f322eb55b17364921cc67de92b3deef59bdf75e2c35db6a97ff7"} [sil-p9628657] Effect of the selective phosphodiesterase type 5 inhibitor sildenafil on erectile dysfunction in the anesthetized dog. (1998). https://pubmed.ncbi.nlm.nih.gov/9628657/ DOI: 10.1016/s0022-5347(01)63097-0

   Complete structured claim and evidence

7. In six HIV-infected patients at steady state on indinavir a single 25 milligram dose of sildenafil did not significantly alter plasma indinavir concentrations, but the geometric mean area under the sildenafil concentration curve of 1631 nanograms per millilitre hour was 4.4 times higher than data from historical controls given either 50 or 100 milligrams and dose normalised to 25 milligrams, and in a parallel study indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro with a half-maximal inhibitory concentration of 0.39 micromolar, so that the mechanism of the increase is inhibition of hepatic metabolism and a lower starting dose may be more appropriate in this setting.

   Indinavir → Sildenafil source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/sildenafil-research/10546851.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504", "start_char": 0, "end_char": 2556, "text_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504"}

   experimental_model

   Open pharmacokinetic study in six patients at steady state on a protease inhibitor, with a parallel in vitro metabolism arm

   exposure

   A single 25 milligram dose of sildenafil added to steady-state indinavir, with plasma sampling to eight hours

   limitations

   Six patients and no concurrent control group: the sildenafil exposure is compared with dose-normalised historical controls rather than with the same patients off indinavir.

   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

   A drug that blocks the same liver enzyme left more than four times as much of it in the blood.

   primary_references

   [sil-p10546851] Interaction of sildenafil and indinavir when co-administered to HIV-positive patients. (1999). https://pubmed.ncbi.nlm.nih.gov/10546851/ DOI: 10.1097/00002030-199910220-00001

   tissue_or_cell_type

   Systemic circulation and liver microsomes

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   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 470–481

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Open pharmacokinetic study in six patients at steady state on a protease inhibitor, with a parallel in vitro metabolism arm · source_derived_draft · unverified_draft

   ### sil-protease-inhibitor-quadruples-exposure In six HIV-infected patients at steady state on indinavir a single 25 milligram dose of sildenafil did not significantly alter plasma indinavir concentrations, but the geometric mean area under the sildenafil concentration curve of 1631 nanograms per millilitre hour was 4.4 times higher than data from historical controls given either 50 or 100 milligrams and dose normalised to 25 milligrams, and in a parallel study indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro with a half-maximal inhibitory concentration of 0.39 micromolar, so that the mechanism of the increase is inhibition of hepatic metabolism and a lower starting dose may be more appropriate in this setting. Condition category: machinery_impairment 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 drug that blocks the same liver enzyme left more than four times as much of it in the blood. organism: Human tissue_or_cell_type: Systemic circulation and liver microsomes experimental_model: Open pharmacokinetic study in six patients at steady state on a protease inhibitor, with a parallel in vitro metabolism arm limitations: Six patients and no concurrent control group: the sildenafil exposure is compared with dose-normalised historical controls rather than with the same patients off indinavir. exposure: A single 25 milligram dose of sildenafil added to steady-state indinavir, with plasma sampling to eight hours evidence_span: {"source_cache": "artifacts/sildenafil-research/10546851.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504", "start_char": 0, "end_char": 2556, "text_sha256": "a789c249a680590fd363d884785a531062441be8e2442ec872fa832dc43b7504"} [sil-p10546851] Interaction of sildenafil and indinavir when co-administered to HIV-positive patients. (1999). https://pubmed.ncbi.nlm.nih.gov/10546851/ DOI: 10.1097/00002030-199910220-00001

   Complete structured claim and evidence

8. Sildenafil alone can cause mean peak reductions in systolic and diastolic blood pressure of 10 and 7 millimetres of mercury that are not dose related while heart rate is unchanged, and sildenafil and nitrates both increase cyclic GMP levels in the systemic circulation but at different points along the nitric oxide to cyclic GMP pathway, so the combination is contraindicated because they synergistically potentiate vasodilation; retrospective analysis of concomitant antihypertensive medications did not indicate an increase in adverse events, and concurrent renal or hepatic impairment or CYP3A4 inhibitors could increase systemic exposure.

   Sildenafil → Cyclic guanosine monophosphate source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/sildenafil-research/10078541.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593", "start_char": 0, "end_char": 2772, "text_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593"}

   experimental_model

   Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance

   exposure

   Sildenafil alone and with antihypertensive classes, across clinical trials and spontaneous reports

   limitations

   A manufacturer-authored review of the development programme rather than an independent analysis, and the post-marketing comparisons are retrospective.

   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

   Both act on the same pathway at different points, which is why together they multiply rather than add.

   primary_references

   [sil-p10078541] Overall cardiovascular profile of sildenafil citrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10078541/ DOI: 10.1016/s0002-9149(99)00046-6

   tissue_or_cell_type

   Cardiovascular system

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   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 431–442

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance · source_derived_draft · unverified_draft

   ### sil-two-points-on-one-pathway Sildenafil alone can cause mean peak reductions in systolic and diastolic blood pressure of 10 and 7 millimetres of mercury that are not dose related while heart rate is unchanged, and sildenafil and nitrates both increase cyclic GMP levels in the systemic circulation but at different points along the nitric oxide to cyclic GMP pathway, so the combination is contraindicated because they synergistically potentiate vasodilation; retrospective analysis of concomitant antihypertensive medications did not indicate an increase in adverse events, and concurrent renal or hepatic impairment or CYP3A4 inhibitors could increase systemic exposure. Condition category: biomarker_context 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: Both act on the same pathway at different points, which is why together they multiply rather than add. organism: Human tissue_or_cell_type: Cardiovascular system experimental_model: Review of the cardiovascular profile from the clinical development programme and post-marketing surveillance limitations: A manufacturer-authored review of the development programme rather than an independent analysis, and the post-marketing comparisons are retrospective. exposure: Sildenafil alone and with antihypertensive classes, across clinical trials and spontaneous reports evidence_span: {"source_cache": "artifacts/sildenafil-research/10078541.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593", "start_char": 0, "end_char": 2772, "text_sha256": "e65228d2afaad9ce38dccf42c7279ec6b562746aa27b121bf5e5782f36cbe593"} [sil-p10078541] Overall cardiovascular profile of sildenafil citrate. (1999). https://pubmed.ncbi.nlm.nih.gov/10078541/ DOI: 10.1016/s0002-9149(99)00046-6

   Complete structured claim and evidence