{"id":"09c5a9bb-4e2f-5082-8030-7bfb7871eea5","stable_key":"252872b9-233f-5692-b72b-c8930ba0cfb7:sil-potentiates-only-the-nerve-signal","predicate":"increases","statement":"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.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"f138009b-b0d4-5eae-bef5-2ec15cb0e16c","mechanism_event_label":"In the living animal it raised nothing by itself and roughly doubled what the nerve was already doing.","subject":{"id":"fe62cf8d-5f89-5e19-bc36-03ad3c9063b7","slug":"sildenafil","display_name":"Sildenafil","entity_type_key":"drug"},"object":{"id":"11d12fb8-1f14-59e2-9d9f-68caab00d655","slug":"intracavernosal-pressure","display_name":"Intracavernosal pressure","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f138009b-b0d4-5eae-bef5-2ec15cb0e16c","stable_key":"252872b9-233f-5692-b72b-c8930ba0cfb7:sil-potentiates-only-the-nerve-signal-event","event_type":"biochemical_relationship","label":"In the living animal it raised nothing by itself and roughly doubled what the nerve was already doing.","description":"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.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"74d8ac3c-c1e9-56bf-a846-86d4a7cf3d28","slug":"pelvic-nerve-stimulation","display_name":"Electrical stimulation of the pelvic nerve","entity_type_key":"cellular_process"},"role":"required_stimulus","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2db51d98-b935-5912-923f-55669e279e49","slug":"l-noarg","display_name":"N-omega-nitro-L-arginine, a nitric oxide synthase inhibitor","entity_type_key":"chemical_species"},"role":"blocking_control","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8a9c57f6-eafd-5243-afaf-d4e830939c4b","slug":"nos3","display_name":"Human endothelial nitric oxide synthase / eNOS / NOS3","entity_type_key":"protein"},"role":"upstream_enzyme","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"736a4c55-284d-5361-bf7a-459544e16af1","slug":"systemic-blood-pressure","display_name":"Systemic arterial blood pressure","entity_type_key":"cellular_process"},"role":"unaffected_measure","stoichiometry":null,"state_label":"","sequence_order":3,"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":4,"notes":""},{"entity":{"id":"11d12fb8-1f14-59e2-9d9f-68caab00d655","slug":"intracavernosal-pressure","display_name":"Intracavernosal pressure","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"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\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Pentobarbital-anaesthetised dogs with pelvic nerve stimulation and nitric oxide synthase inhibition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Intravenous sildenafil 1 to 100 micrograms per kilogram, with N-omega-nitro-L-arginine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"An in vivo test of the amplifier principle with the nitric oxide synthase inhibitor as the control. Anaesthetised animals.","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":"Dog","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"In the living animal it raised nothing by itself and roughly doubled what the nerve was already doing.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Corpus cavernosum and systemic circulation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"1e9c6b29-b4f3-5b7e-8798-e9bed7f9af8a","evidence_kind":"source_excerpt","locator":"Lines 301-312","start_line":301,"end_line":312,"excerpt":"### sil-potentiates-only-the-nerve-signal\nThe 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.\nCondition category: biomarker_context\nnutrient_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.\nplain_language: In the living animal it raised nothing by itself and roughly doubled what the nerve was already doing.\norganism: Dog\ntissue_or_cell_type: Corpus cavernosum and systemic circulation\nexperimental_model: Pentobarbital-anaesthetised dogs with pelvic nerve stimulation and nitric oxide synthase inhibition\nlimitations: An in vivo test of the amplifier principle with the nitric oxide synthase inhibitor as the control. Anaesthetised animals.\nexposure: Intravenous sildenafil 1 to 100 micrograms per kilogram, with N-omega-nitro-L-arginine\nevidence_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\"}\n[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","model_system":"Pentobarbital-anaesthetised dogs with pelvic nerve stimulation and nitric oxide synthase inhibition","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c6c2a590-1f8f-5fac-b2c7-3aae0440b9fd","stable_key":"import-252872b9-233f-5692-b72b-c8930ba0cfb7","title":"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)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"bc81793d20d20d2eaad9cb530b70695d8d8778a3d7136e24715ac3369b939953","revision_id":"301732e1-2446-5b67-b3bd-580164b85b05","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}