{"doi":"10.1161/01.hyp.19.6.692","title":"In vivo metabolism of angiotensin I by neutral endopeptidase (EC 3.4.24.11) in spontaneously hypertensive rats.","abstract":"<jats:p>We investigated the processing enzymes involved in the formation of circulating angiotensin-(1-7) after intravenous administration of angiotensin I to conscious spontaneously hypertensive and Wistar-Kyoto rats. Immunoreactive products, including angiotensin I, angiotensin II, and angiotensin-(1-7), were measured in arterial blood by three specific radioimmunoassays. Angiotensin I infusion (2 nmol) induced a rapid increase in immunoreactive angiotensin II and angiotensin-(1-7). Pretreatment with the angiotensin converting enzyme inhibitor enalaprilat (2 mg/kg) eliminated angiotensin II formation and augmented circulating levels of angiotensin I and angiotensin-(1-7) in spontaneously hypertensive and Wistar-Kyoto rats. The elevated levels of angiotensin-(1-7) in enalaprilat-treated rats were blocked by concurrent treatment with the neutral endopeptidase (EC 3.4.24.11) inhibitor SCH 39,370 (15 mg/kg) in both strains. Administration of SCH 39,370 alone decreased angiotensin-(1-7) levels in spontaneously hypertensive rats, whereas angiotensin II levels increased in both strains (p less than 0.01). Comparisons of the metabolism of angiotensin I in the two rat strains showed increased formation of angiotensin-(1-7) in spontaneously hypertensive rats not given any of the enzyme inhibitors. In addition, levels of angiotensin I were higher after administration of SCH 39,370 in hypertensive rats. These novel findings reveal that neutral endopeptidase EC 3.4.24.11 participates in the conversion of angiotensin I to angiotensin-(1-7) and in the metabolism of angiotensin II in the circulation of both spontaneously hypertensive and Wistar-Kyoto rats. Our results suggest that neutral endopeptidase EC 3.4.24.11 is a major enzymatic constituent of the circulating renin-angiotensin system.</jats:p>","journal":"Hypertension","year":1992,"id":16481,"datarank":7.272801706158861,"base_score":5.247024072160486,"endowment":5.247024072160486,"self_citation_contribution":0.787053610824073,"citation_network_contribution":6.485748095334787,"self_endowment_contribution":0.787053610824073,"citer_contribution":6.485748095334787,"corpus_percentile":null,"corpus_rank":null,"citation_count":189,"citer_count":148,"citers_with_citation_signal":136,"citers_with_endowment":136,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":121494,"name":"M C Chappell","orcid":null,"position":1,"is_corresponding":false},{"id":121495,"name":"K B Brosnihan","orcid":null,"position":2,"is_corresponding":false},{"id":121496,"name":"C M Ferrario","orcid":null,"position":3,"is_corresponding":false},{"id":121153,"name":"K Yamamoto","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.247024072160486,"endowment":5.247024072160486,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"1317352","pmcid":null,"openalex_id":"https://openalex.org/W2013183546","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL-6835","title":null}],"total_grants":1,"fwci":1.7256,"citation_percentile":0.84552037,"influential_citations":5,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":13},{"year":2014,"count":7},{"year":2015,"count":5},{"year":2016,"count":2},{"year":2017,"count":5},{"year":2018,"count":2},{"year":2019,"count":5},{"year":2020,"count":11},{"year":2021,"count":6},{"year":2022,"count":4},{"year":2023,"count":4},{"year":2024,"count":5},{"year":2025,"count":1},{"year":2026,"count":3}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.ahajournals.org/doi/pdf/10.1161/01.HYP.19.6.692","host_type":"publisher"},{"url":"https://doi.org/10.1161/01.hyp.19.6.692","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/1317352","host_type":"repository"}],"fields_of_study":["Receptor Mechanisms and Signaling","Pharmacogenetics and Drug Metabolism","Hormonal Regulation and Hypertension","Chemistry","Medicine","Angiotensin I","Angiotensin II","Angiotensin-Converting Enzyme Inhibitors","Animals","Enalaprilat","Endopeptidases","Hypertension","Male","Neprilysin","Osmolar Concentration","Peptide Fragments","Prolyl Oligopeptidases","Rats","Rats, Inbred SHR","Rats, Inbred WKY","Serine Endopeptidases","Time Factors"],"mesh_terms":["Prolyl Oligopeptidases","Angiotensin I","Angiotensin II","Angiotensin-Converting Enzyme Inhibitors","Animals","Hypertension","Male","Osmolar Concentration","Peptide Fragments","Endopeptidases","Rats, Inbred SHR","Rats, Inbred WKY","Serine Endopeptidases","Time Factors","Neprilysin","Enalaprilat","Rats"],"keywords":["Enalaprilat","Angiotensin II","Renin–angiotensin system","Internal medicine","Endocrinology","Angiotensin-converting enzyme","Angiotensin II receptor type 1","Neprilysin","Chemistry","Angiotensin receptor","Losartan","Angiotensin III","ACE inhibitor","Enzyme","Medicine","Blood pressure","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-02T09:21:38.587905Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}