{"id":"1d938bd9-7828-587a-bd28-7d9d1e7b25c1","stable_key":"252872b9-233f-5692-b72b-c8930ba0cfb7:sil-conduit-arteries-relax-too","predicate":"increases","statement":"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.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"adee8c63-94d3-5d3b-9074-1e85cd281606","mechanism_event_label":"The same direct relaxation appears in the arteries used for bypass grafts, and it too survives blocking nitric oxide synthesis.","subject":{"id":"fe62cf8d-5f89-5e19-bc36-03ad3c9063b7","slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"},"object":{"id":"99ca0abf-ccf7-50a8-9246-e75009b035e3","slug":"coronary-artery","display_name":"Coronary and internal mammary and radial arteries","entity_type_key":"tissue"},"evidence_count":1,"mechanism_event":{"id":"adee8c63-94d3-5d3b-9074-1e85cd281606","stable_key":"252872b9-233f-5692-b72b-c8930ba0cfb7:sil-conduit-arteries-relax-too-event","event_type":"observed_intervention","label":"The same direct relaxation appears in the arteries used for bypass grafts, and it too survives blocking nitric oxide synthesis.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"28da2e26-907c-530b-bd0e-4f71928d6e92","slug":"l-nmma","display_name":"NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor","entity_type_key":"chemical_species"},"role":"ineffective_blocker","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e24cdc15-76b3-5898-a42d-632275759a0b","slug":"sodium-nitroprusside","display_name":"Sodium nitroprusside","entity_type_key":"chemical_species"},"role":"amplified_donor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"1f255446-9b28-5dd9-87de-d50f236055f4","slug":"vascular-smooth-muscle","display_name":"Vascular smooth muscle","entity_type_key":"cell_type"},"role":"affected_tissue","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"fe62cf8d-5f89-5e19-bc36-03ad3c9063b7","slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"99ca0abf-ccf7-50a8-9246-e75009b035e3","slug":"coronary-artery","display_name":"Coronary and internal mammary and radial arteries","entity_type_key":"tissue"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Organ bath studies on coronary, internal mammary and radial arteries and forearm veins from sixteen multiorgan donors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Sildenafil from 10 nanomolar to 30 micromolar on precontracted vessels, with nitric oxide synthase inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":{"slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The same direct relaxation appears in the arteries used for bypass grafts, and it too survives blocking nitric oxide synthesis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sil-p11081893] Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels. 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Again the upper concentrations are far above therapeutic and the relaxation in coronary artery was modest.\nexposure: Sildenafil from 10 nanomolar to 30 micromolar on precontracted vessels, with nitric oxide synthase inhibition\nevidence_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\"}\n[sil-p11081893] Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels. 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