{"doi":"10.1152/jappl.1995.79.6.2122","title":"Endothelin-receptor antagonist bosentan prevents and reverses hypoxic pulmonary hypertension in rats","abstract":"<jats:p> The current study examined the effects of bosentan, an orally active antagonist of endothelin-A and -B receptors, on the development and maintenance of hypoxia (10% O2)-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with bosentan (100 mg.kg-1.day-1, 1 gavage/day for 2 days) completely blocked the pulmonary vasoconstrictor response to acute hypoxia. Chronic bosentan treatment (100 mg.kg-1.day-1 po in the food) instituted 48 h before hypoxic exposure prevented the subsequent development of pulmonary hypertension, attenuated the associated right heart hypertrophy, and prevented the remodeling of small (50–100 microns) pulmonary arteries without altering systemic arterial pressure. Institution of bosentan treatment (for 4 wk) after 2 wk of hypoxia produced a significant reversal of established hypoxia-induced pulmonary hypertension (from 36 +/- 1 to 25 +/- 1 mmHg), right heart hypertrophy, and pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous endothelin-1 plays a major role in hypoxic pulmonary vasoconstriction and/or hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that endothelin-receptor blockade may be useful in the treatment of hypoxic pulmonary hypertension humans. </jats:p>","journal":"Journal of Applied Physiology","year":1995,"id":28977,"datarank":13.338972800872845,"base_score":5.697093486505405,"endowment":5.697093486505405,"self_citation_contribution":0.8545640229758108,"citation_network_contribution":12.484408777897034,"self_endowment_contribution":0.8545640229758108,"citer_contribution":12.484408777897034,"corpus_percentile":null,"corpus_rank":null,"citation_count":297,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"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":160889,"name":"Y. F. Chen","orcid":null,"position":1,"is_corresponding":false},{"id":160890,"name":"Q. C. Meng","orcid":null,"position":2,"is_corresponding":false},{"id":160891,"name":"J. Durand","orcid":null,"position":3,"is_corresponding":false},{"id":160892,"name":"V. S. Dicarlo","orcid":null,"position":4,"is_corresponding":false},{"id":160893,"name":"S. Oparil","orcid":null,"position":5,"is_corresponding":false},{"id":25743,"name":"S. J. Chen","orcid":"0000-0003-0447-5348","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.697093486505405,"endowment":5.697093486505405,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"8847282","pmcid":null,"openalex_id":"https://openalex.org/W2104172548","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL-44195","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL-48848","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL-47081","title":null}],"total_grants":3,"fwci":9.9887,"citation_percentile":0.98419009,"influential_citations":6,"citation_trend":[{"year":2012,"count":7},{"year":2013,"count":10},{"year":2014,"count":7},{"year":2015,"count":7},{"year":2016,"count":4},{"year":2018,"count":3},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2021,"count":3},{"year":2022,"count":7},{"year":2023,"count":2},{"year":2024,"count":3},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.physiology.org/doi/pdf/10.1152/jappl.1995.79.6.2122","host_type":"publisher"},{"url":"https://doi.org/10.1152/jappl.1995.79.6.2122","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/8847282","host_type":"repository"}],"fields_of_study":["Pulmonary Hypertension Research and Treatments","Eicosanoids and Hypertension Pharmacology","Nitric Oxide and Endothelin Effects","Medicine","Animals","Blood Pressure","Bosentan","Heart Rate","Hypertension, Pulmonary","Hypoxia","Male","Pulmonary Circulation","Rats","Rats, Sprague-Dawley","Sulfonamides","Time Factors"],"mesh_terms":["Bosentan","Animals","Hypoxia","Blood Pressure","Heart Rate","Hypertension, Pulmonary","Male","Pulmonary Circulation","Sulfonamides","Time Factors","Rats, Sprague-Dawley","Rats"],"keywords":["Bosentan","Endothelin receptor antagonist","Pulmonary hypertension","Endothelin receptor","Medicine","Antagonist","Internal medicine","Endothelin 1","Hypoxia (environmental)","Endocrinology","Receptor antagonist","Pharmacology","Cardiology","Receptor","Chemistry"],"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":"2026-06-08T22:27:43.187286Z","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":[]}