Sodium nitroprusside

evidence_access

Primary abstract

experimental_model

Rat UMR106 and mouse MC3T3-E1 culture program.

limitations

Mimicry is not equivalent to selective blockade and rescue of the proposed vanadate mechanism.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

A donor experiment supports a possible downstream mediator.

primary_references

Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10988345/ · DOI 10.1016/s0014-2999(00)00356-3

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 334–340

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat UMR106 and mouse MC3T3-E1 culture program. · source_derived_draft · unverified_draft

## vanadium-bone-no-donor A donor experiment supports a possible downstream mediator. The NO donor sodium nitroprusside reduced growth and alkaline-phosphatase activity, mimicking part of the vanadate phenotype. Model: Rat UMR106 and mouse MC3T3-E1 culture program. Limitations: Mimicry is not equivalent to selective blockade and rescue of the proposed vanadate mechanism. Evidence access: Primary abstract Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10988345/ · DOI 10.1016/s0014-2999(00)00356-3

evidence_span

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experimental_model

Organ bath studies on coronary, internal mammary and radial arteries and forearm veins from sixteen multiorgan donors

exposure

Sildenafil from 10 nanomolar to 30 micromolar on precontracted vessels, with nitric oxide synthase inhibition

limitations

Extends the same finding to conduit arteries used in bypass surgery. Again the upper concentrations are far above therapeutic and the relaxation in coronary artery was modest.

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

The same direct relaxation appears in the arteries used for bypass grafts, and it too survives blocking nitric oxide synthesis.

primary_references

[sil-p11081893] Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels. (2000). https://pubmed.ncbi.nlm.nih.gov/11081893/ DOI: 10.1016/s0003-4975(00)01914-7

tissue_or_cell_type

Arterial and venous conduits

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 366–377

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organ bath studies on coronary, internal mammary and radial arteries and forearm veins from sixteen multiorgan donors · source_derived_draft · unverified_draft

### sil-conduit-arteries-relax-too Sildenafil from 10 nanomolar to 30 micromolar caused concentration-dependent relaxation in internal mammary arteries, radial arteries and forearm veins with a modest relaxant effect in coronary arteries, amplified the relaxation induced by sodium nitroprusside in all four vessels, and relaxation was unaffected by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine at 100 micromolar, the drug being eight to ten times more potent than zaprinast. 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: The same direct relaxation appears in the arteries used for bypass grafts, and it too survives blocking nitric oxide synthesis. organism: Human tissue_or_cell_type: Arterial and venous conduits experimental_model: Organ bath studies on coronary, internal mammary and radial arteries and forearm veins from sixteen multiorgan donors limitations: Extends the same finding to conduit arteries used in bypass surgery. Again the upper concentrations are far above therapeutic and the relaxation in coronary artery was modest. exposure: Sildenafil from 10 nanomolar to 30 micromolar on precontracted vessels, with nitric oxide synthase inhibition evidence_span: {"source_cache": "artifacts/sildenafil-research/11081893.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7425aaede1777ba3689df435384bb535635a8181487b1937154eb635a01c9dbb", "start_char": 0, "end_char": 1602, "text_sha256": "7425aaede1777ba3689df435384bb535635a8181487b1937154eb635a01c9dbb"} [sil-p11081893] Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels. (2000). https://pubmed.ncbi.nlm.nih.gov/11081893/ DOI: 10.1016/s0003-4975(00)01914-7

evidence_span

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experimental_model

Organ bath studies on penile dorsal arteries and deep dorsal veins from fourteen multiorgan donors

exposure

Sildenafil from 1 nanomolar to 3 micromolar on precontracted vessels, with nitric oxide synthase inhibition and electrical field stimulation

limitations

Tests whether the drug relaxes vessels when nitric oxide synthesis is blocked, and finds that it does. The concentrations reach the micromolar range, well above those active on the enzyme.

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 these vessels the drug relaxed them by itself even with nitric oxide synthesis blocked.

primary_references

[sil-p10962340] Effects of sildenafil on human penile blood vessels. (2000). https://pubmed.ncbi.nlm.nih.gov/10962340/ DOI: 10.1016/s0090-4295(00)00622-1

tissue_or_cell_type

Penile blood vessels

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 353–364

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organ bath studies on penile dorsal arteries and deep dorsal veins from fourteen multiorgan donors · source_derived_draft · unverified_draft

### sil-direct-relaxation-survives-nos-block In human penile dorsal arteries and deep dorsal veins sildenafil from 1 nanomolar to 3 micromolar caused concentration-dependent relaxation and amplified the relaxation induced by sodium nitroprusside, and this relaxation was unaffected by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine at 100 micromolar, while electrical field stimulation contractions were attenuated by sildenafil and nitric-oxide-dependent relaxations after guanethidine were enhanced. 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 these vessels the drug relaxed them by itself even with nitric oxide synthesis blocked. organism: Human tissue_or_cell_type: Penile blood vessels experimental_model: Organ bath studies on penile dorsal arteries and deep dorsal veins from fourteen multiorgan donors limitations: Tests whether the drug relaxes vessels when nitric oxide synthesis is blocked, and finds that it does. The concentrations reach the micromolar range, well above those active on the enzyme. exposure: Sildenafil from 1 nanomolar to 3 micromolar on precontracted vessels, with nitric oxide synthase inhibition and electrical field stimulation evidence_span: {"source_cache": "artifacts/sildenafil-research/10962340.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4bffd4647ca406d3c452e47c7dad6e70ebcc98e4ff4145bc5510b97c38109f1b", "start_char": 0, "end_char": 1577, "text_sha256": "4bffd4647ca406d3c452e47c7dad6e70ebcc98e4ff4145bc5510b97c38109f1b"} [sil-p10962340] Effects of sildenafil on human penile blood vessels. (2000). https://pubmed.ncbi.nlm.nih.gov/10962340/ DOI: 10.1016/s0090-4295(00)00622-1

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

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experimental_model

Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina

exposure

Sildenafil with and without nitric oxide drive, and against glyceryl trinitrate, sodium nitroprusside and milrinone

limitations

The single most complete pharmacological characterisation here, covering the target, the absence of effect without upstream drive, the nitrate potentiation, the absence of an inotropic effect, and the retinal effect in one series.

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, rabbit and dog

plain_language

With no signal present the drug does nothing; its entire action is to keep an existing signal from being cleared.

primary_references

[sil-p10629850] The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. (1999). https://pubmed.ncbi.nlm.nih.gov/10629850/ DOI: 10.1254/fpj.114.supplement_22

tissue_or_cell_type

Corpus cavernosum, aorta, cardiac trabeculae and retina

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 262–273

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina · source_derived_draft · unverified_draft

### sil-no-effect-without-nitric-oxide Sildenafil is a potent competitive inhibitor of PDE5 with a half-maximal inhibitory concentration of 3.5 nanomolar, selective over PDE1 to PDE4 by 80 to 19,000-fold and over retinal PDE6 by 10-fold, it enhanced cyclic GMP accumulation driven with sodium nitroprusside in rabbit corpus cavernosum without affecting cyclic AMP, and in the absence of nitric oxide drive it had no functional effect on human and rabbit isolated corpus cavernosum but potently potentiated the relaxant effects of nitric oxide on these tissues. 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: With no signal present the drug does nothing; its entire action is to keep an existing signal from being cleared. organism: Human, rabbit and dog tissue_or_cell_type: Corpus cavernosum, aorta, cardiac trabeculae and retina experimental_model: Enzyme selectivity panel with isolated tissue, anaesthetised dog haemodynamics and isolated retina limitations: The single most complete pharmacological characterisation here, covering the target, the absence of effect without upstream drive, the nitrate potentiation, the absence of an inotropic effect, and the retinal effect in one series. exposure: Sildenafil with and without nitric oxide drive, and against glyceryl trinitrate, sodium nitroprusside and milrinone evidence_span: {"source_cache": "artifacts/sildenafil-research/10629850.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92", "start_char": 0, "end_char": 2057, "text_sha256": "af056c516b44e35eac7b0511ba3a8403ed84c347af6094ebc153f68c8ee7db92"} [sil-p10629850] The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. (1999). https://pubmed.ncbi.nlm.nih.gov/10629850/ DOI: 10.1254/fpj.114.supplement_22

evidence_span

{"source_cache": "artifacts/sildenafil-research/10078537.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5", "start_char": 0, "end_char": 2610, "text_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5"}

experimental_model

Immunochemical distribution of phosphodiesterase activity across human tissues with isolated organ bath studies and platelet aggregometry

exposure

Anti-PDE1 and anti-PDE5 antibodies with functional testing, and sildenafil against sodium nitroprusside on platelets

limitations

Maps where the target enzyme is and is not, which is what predicts where the drug acts. Antibody-based detection, so absence of signal is weaker evidence than presence.

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, rabbit and dog

plain_language

Platelets carry the same enzyme, and again the drug does nothing to them until a nitric oxide donor is present.

primary_references

[sil-p10078537] Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. (1999). https://pubmed.ncbi.nlm.nih.gov/10078537/ DOI: 10.1016/s0002-9149(99)00042-9

tissue_or_cell_type

Cardiac ventricle, saphenous vein, mesenteric artery, corpus cavernosum and platelets

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 327–338

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immunochemical distribution of phosphodiesterase activity across human tissues with isolated organ bath studies and platelet aggregometry · source_derived_draft · unverified_draft

### sil-platelets-need-a-donor-too Human platelets were found to contain PDE5 which was inhibited by sildenafil with a half-maximal inhibitory concentration of 6.3 nanomolar consistent with the value in corpus cavernosum, sildenafil alone had no direct effect on platelet function but it potentiated the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human platelets, and in phenylephrine-contracted rabbit aortic rings it enhanced glyceryl trinitrate relaxation. 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: Platelets carry the same enzyme, and again the drug does nothing to them until a nitric oxide donor is present. organism: Human, rabbit and dog tissue_or_cell_type: Cardiac ventricle, saphenous vein, mesenteric artery, corpus cavernosum and platelets experimental_model: Immunochemical distribution of phosphodiesterase activity across human tissues with isolated organ bath studies and platelet aggregometry limitations: Maps where the target enzyme is and is not, which is what predicts where the drug acts. Antibody-based detection, so absence of signal is weaker evidence than presence. exposure: Anti-PDE1 and anti-PDE5 antibodies with functional testing, and sildenafil against sodium nitroprusside on platelets evidence_span: {"source_cache": "artifacts/sildenafil-research/10078537.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5", "start_char": 0, "end_char": 2610, "text_sha256": "dceb60af4400fe67b4ffaf73a0aadb8d2e5fad0966b3372a3e46a91c0e0ccee5"} [sil-p10078537] Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. (1999). https://pubmed.ncbi.nlm.nih.gov/10078537/ DOI: 10.1016/s0002-9149(99)00042-9