{"doi":"10.20944/preprints202407.1135.v1","title":"Sacubitril/Valsartan Combination Partially Improves Cardiac Systolic Function through β<sub>1</sub>-/β<sub>2</sub>-AR Responsiveness but Not Diastolic Function in a Rat Model of Type 2 Diabetes","abstract":"Cardiovascular complications are the major cause of diabetes-related morbidity and mortality. Increased renin-angiotensin-aldosterone system activity and decreased β-adrenergic receptor (β-AR) responsiveness contribute to diabetic cardiac dysfunction. We evaluated the effect of sacubitril/valsartan (neprilysin inhibitor plus angiotensin receptor antagonist combination), and valsartan treatments on the diabetic cardiac function through β-AR responsiveness, and on protein expression of diastolic components. 6-week-old male Sprague-Dawley rats were divided into control, diabetic, sacubitril/valsartan (68 mg/kg), and valsartan treated (31 mg/kg) diabetic groups. Diabetes was induced by high fat diet plus low dose streptozotocin (30 mg/kg, intraperitoneal). After 10 weeks of diabetes, rats were treated for 4 weeks. Systolic/diastolic function was assessed by in vivo echocardiography and pressure-volume loop analysis. β-AR mediated responsiveness was assessed by in vitro papillary muscle and Langendorff heart experiments. Protein expression of sarcoplasmic reticulum calcium ATPase2a, phospholamban, and phosphorylated phospholamban was determined by Western blot. Sacubitril/valsartan improved ejection fraction and fractional shortening to a similar extent as valsartan alone. None of the treatments affected in vivo diastolic parameters or expression of related proteins. β1-/β2-AR mediated responsiveness was partially restored in treated animals. β3-AR mediated relaxation responses were comparable among groups. The beneficial effect of sacubitril/valsartan on systolic function may be attributed to improved β1-/β2-AR responsiveness.","journal":"Preprints.org","year":2024,"id":491409,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1337010,"name":"Zeynep Elif Yeşilyurt","orcid":"0000-0001-5659-8839","position":1,"is_corresponding":false},{"id":1337368,"name":"Irem Karaomerlioglu","orcid":null,"position":2,"is_corresponding":false},{"id":1337011,"name":"A. Elif Müderrisoglu","orcid":"0000-0002-2027-0118","position":3,"is_corresponding":false},{"id":1337012,"name":"Kadir Sevim","orcid":"0000-0002-1959-1010","position":4,"is_corresponding":false},{"id":118934,"name":"Martin C. Michel","orcid":"0000-0003-4161-8467","position":5,"is_corresponding":false},{"id":1337013,"name":"Ebru Arioglu‐Inan","orcid":"0000-0002-0860-0815","position":6,"is_corresponding":false},{"id":1337009,"name":"Betül Rabia Erdoğan","orcid":"0000-0001-7377-4777","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:08:45.247225Z","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,"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":[]}