Sacubitril/valsartan combination partially improves cardiac systolic, but not diastolic, function through β-ar responsiveness in a rat model of type 2 diabetes
| dc.contributor.author | Erdoğan, Betül Rabia | |
| dc.contributor.author | Yeşilyurt Dirican, Zeynep Elif | |
| dc.contributor.author | Karaömerlioğlu, İrem | |
| dc.contributor.author | Müderrisoğlu, Ayhanım Elif | |
| dc.contributor.author | Sevim, Kadir | |
| dc.contributor.author | Michel, Martin | |
| dc.contributor.author | Arıoğlu İnan, Ebru | |
| dc.date.accessioned | 2025-10-06T08:18:30Z | |
| dc.date.available | 2025-10-06T08:18:30Z | |
| dc.date.issued | 2024 | |
| dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalı | |
| dc.description.abstract | Cardiovascular complications are the major cause of diabetes mellitus-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. Six-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 a 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 the expression of related proteins. β1-/β2-AR-mediated responsiveness was partially restored in treated animals. β3-AR-mediated cardiac relaxation (an indicator of diastolic function) responses were comparable among groups. The beneficial effect of sacubitril/valsartan on systolic function may be attributed to improved β1-/β2-AR responsiveness. | |
| dc.description.sponsorship | Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TÜBİTAK) ; Ankara University | |
| dc.identifier.citation | Erdoğan, B. R., Yeşilyurt Dirican, Z. E., Karaömerlioğlu, İ., Müderrisoğlu, A. E., Sevim, K., Michel, M. ... Arıoğlu İnan, E. (2024). Sacubitril/valsartan combination partially improves cardiac systolic, but not diastolic, function through β-ar responsiveness in a rat model of type 2 diabetes. International Journal of Molecular Sciences, 25(19). http://dx.doi.org/10.3390/ijms251910617 | |
| dc.identifier.doi | 10.3390/ijms251910617 | |
| dc.identifier.issn | 1661-6596 | |
| dc.identifier.issn | 1422-0067 | |
| dc.identifier.issue | 19 | |
| dc.identifier.pmid | 39408945 | |
| dc.identifier.scopus | 2-s2.0-85206294613 | |
| dc.identifier.scopusquality | Q1 | |
| dc.identifier.uri | http://dx.doi.org/10.3390/ijms251910617 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12511/13074 | |
| dc.identifier.volume | 25 | |
| dc.identifier.wos | WOS:001332368300001 | |
| dc.identifier.wosquality | Q1 | |
| dc.indekslendigikaynak | Web of Science | |
| dc.indekslendigikaynak | Scopus | |
| dc.indekslendigikaynak | PubMed | |
| dc.institutionauthor | Müderrisoğlu, Ayhanım Elif | |
| dc.language.iso | en | |
| dc.relation.ispartof | International Journal of Molecular Sciences | |
| dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | |
| dc.relation.tubitak | info:eu-repo/grantAgreement/TUBITAK/SOBAG/117S936 | |
| dc.relation.tubitak | info:eu-repo/grantAgreement/TUBITAK/SOBAG/115S564 | |
| dc.relation.tubitak | info:eu-repo/grantAgreement/TUBITAK/SOBAG/19H0237004 | |
| dc.relation.tubitak | info:eu-repo/grantAgreement/TUBITAK/SOBAG/2211/A | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.subject | Diabetes | |
| dc.subject | Heart | |
| dc.subject | Sacubitril | |
| dc.subject | Valsartan | |
| dc.subject | Β-Adrenoceptor | |
| dc.title | Sacubitril/valsartan combination partially improves cardiac systolic, but not diastolic, function through β-ar responsiveness in a rat model of type 2 diabetes | |
| dc.type | Article |
