NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor: molecular mechanisms & dependencies

How nutrients influence it

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Human evidence only

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What it does

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Recorded relationships

Where it participates (unsigned role)

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.
Sildenafil → Coronary and internal mammary and radial arteries source_derived_draftungraded
Experimental context and source evidence
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"}
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
Complete structured claim and evidence
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.
Sildenafil → Relaxation of vascular and trabecular smooth muscle source_derived_draftungraded
Experimental context and source evidence
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"}
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
Complete structured claim and evidence

The events it takes part in

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Situations it appears in

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In the sources

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Open hypotheses

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This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor