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Sacubitril/Valsartan Combination Partially Improves Cardiac Systolic Function through β1-/β2-AR Responsiveness but Not Diastolic Function in a Rat Model of Type 2 Diabetes
Version 1
: Received: 12 July 2024 / Approved: 15 July 2024 / Online: 15 July 2024 (08:04:31 CEST)
How to cite:
Erdogan, B. R.; Yesilyurt-Dirican, Z. E.; Karaomerlioglu, I.; Muderrisoglu, A. E.; Sevim, K.; Michel, M. C.; Arioglu-Inan, E. Sacubitril/Valsartan Combination Partially Improves Cardiac Systolic Function through β1-/β2-AR Responsiveness but Not Diastolic Function in a Rat Model of Type 2 Diabetes. Preprints2024, 2024071135. https://doi.org/10.20944/preprints202407.1135.v1
Erdogan, B. R.; Yesilyurt-Dirican, Z. E.; Karaomerlioglu, I.; Muderrisoglu, A. E.; Sevim, K.; Michel, M. C.; Arioglu-Inan, E. Sacubitril/Valsartan Combination Partially Improves Cardiac Systolic Function through β1-/β2-AR Responsiveness but Not Diastolic Function in a Rat Model of Type 2 Diabetes. Preprints 2024, 2024071135. https://doi.org/10.20944/preprints202407.1135.v1
Erdogan, B. R.; Yesilyurt-Dirican, Z. E.; Karaomerlioglu, I.; Muderrisoglu, A. E.; Sevim, K.; Michel, M. C.; Arioglu-Inan, E. Sacubitril/Valsartan Combination Partially Improves Cardiac Systolic Function through β1-/β2-AR Responsiveness but Not Diastolic Function in a Rat Model of Type 2 Diabetes. Preprints2024, 2024071135. https://doi.org/10.20944/preprints202407.1135.v1
APA Style
Erdogan, B. R., Yesilyurt-Dirican, Z. E., Karaomerlioglu, I., Muderrisoglu, A. E., Sevim, K., Michel, M. C., & Arioglu-Inan, E. (2024). 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. Preprints. https://doi.org/10.20944/preprints202407.1135.v1
Chicago/Turabian Style
Erdogan, B. R., Martin C. Michel and Ebru Arioglu-Inan. 2024 "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" Preprints. https://doi.org/10.20944/preprints202407.1135.v1
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.
Medicine and Pharmacology, Cardiac and Cardiovascular Systems
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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