{"doi":"10.1093/ajh/hpaf033","title":"Oral Losartan Treatment Improves Microvascular Endothelial Function via Nitric Oxide-Dependent Mechanisms in Women With a History of Preeclampsia","abstract":"BACKGROUND: Women with a history of preeclampsia are at increased risk of developing cardiovascular disease compared with women who had a healthy pregnancy. One potential mechanism underlying this increased risk is microvascular endothelial dysfunction, characterized by reduced nitric oxide (NO)-dependent dilation and is mediated, in part, by increased vasoconstrictor sensitivity to angiotensin II, which persists postpartum. We hypothesized that systemic angiotensin II type 1 receptor (AT1R) inhibition via once-daily oral losartan treatment would (1) improve endothelium- and NO-dependent dilation, and (2) reduce angiotensin II-mediated vasoconstriction, in the microvasculature of women with a history of preeclampsia. METHODS: Eleven normotensive women, >12 weeks and ≤5 years postpartum, with a history of preeclampsia participated in a double-blind, placebo-controlled, crossover study. Following 6 weeks of placebo and losartan treatment (50 mg/day), we measured cutaneous vascular conductance responses to graded infusions of acetylcholine (ACh, 10-10-10-1 M) alone or with 15 mM NG-nitro-l-arginine methyl ester (L-NAME; NO-synthase inhibitor) to assess endothelium- and NO-dependent dilation, respectively. We also assessed microvascular vasoconstrictor responses to graded infusions of angiotensin II (10-20-10-4 M) and norepinephrine (10-12-10-2 M). RESULTS: Losartan treatment increased endothelium- (P < 0.001) and NO-dependent (P < 0.016) vasodilation compared with placebo. Losartan treatment also reduced angiotensin II-mediated vasoconstriction (P < 0.001) compared with placebo, but had no effect on norepinephrine-mediated vasoconstriction (P = 0.46). CONCLUSIONS: These data suggest that systemic AT1R-inhibition with oral losartan is a viable, mechanism-specific approach to improve endothelial function and reduce vasoconstrictor sensitivity to angiotensin II in the microvasculature of healthy, normotensive women with a history of preeclampsia.","journal":"American Journal of Hypertension","year":2025,"id":531193,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232869,"name":"Diana Jalal","orcid":"0000-0002-1975-8650","position":1,"is_corresponding":false},{"id":411052,"name":"Anna E. Stanhewicz","orcid":"0000-0002-3941-3879","position":2,"is_corresponding":false},{"id":1263092,"name":"Kelsey Schwartz","orcid":"0000-0002-1418-1813","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T02:51:14.579161Z","pmid":"40077915","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":[]}