{"doi":"10.3389/fphys.2022.876777","title":"Estrogen Metabolite 2-Methoxyestradiol Attenuates Blood Pressure in Hypertensive Rats by Downregulating Angiotensin Type 1 Receptor","abstract":"The therapeutic potential of 2-Methoxyestradiol (2ME2) is evident in cardiovascular disease. Our laboratory has previously demonstrated the mechanism involved in the 2ME2 regulation of angiotensin type 1 receptor (AT1R) in vitro . However, 2ME2 regulation of angiotensin receptors and its effects on blood pressure (BP) and resting heart rate (RHR) are uncertain. In this study, male and female Wistar-Kyoto (WKY) rats infused with angiotensin II (65 ng/min) and male spontaneously hypertensive rats (SHR) were surgically implanted with telemetric probes to continuously assess arterial BP and RHR. In both male and female WKY rats, 2ME2 treatment (20 mg/kg/day for 2 weeks) resulted in a significant reduction of Ang II-induced systolic, diastolic, and mean arterial BP. Moreover, significant weight loss and RHR were indicated in all groups. In a separate set of experiments, prolonged 2ME2 exposure in male SHR (20 mg/kg/day for 5 weeks) displayed a significant reduction in diastolic and mean arterial BP along with RHR. We also found downregulation of angiotensin receptors and angiotensinogen (AGT) in the kidney and liver and a reduction of plasma Ang II levels. Collectively, we demonstrate that 2ME2 attenuated BP and RHR in hypertensive rats involves downregulation of angiotensin receptors and body weight loss.","journal":"Frontiers in Physiology","year":2022,"id":288107,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":688428,"name":"Benard O. Ogola","orcid":"0000-0002-6084-6986","position":1,"is_corresponding":false},{"id":367500,"name":"Laxmi Iyer","orcid":"0000-0001-9218-4481","position":2,"is_corresponding":false},{"id":921491,"name":"Vardan T. Karamyan","orcid":"0000-0003-0050-6047","position":3,"is_corresponding":false},{"id":968542,"name":"Thomas Thekkumkara","orcid":"0000-0001-8865-1446","position":4,"is_corresponding":false},{"id":968541,"name":"Yong Zhang","orcid":"0000-0002-7084-9849","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T00:30:11.069895Z","pmid":"35586713","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,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}