Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway
Empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, prevents endothelial dysfunction, but its effects on vascular tone in hypertension remain unclear. This study investigated whether EMPA modulates vasomotor tone via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) pa...
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2025-03-01
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| author | Monika Kloza Anna Krzyżewska Hanna Kozłowska Sandra Budziak Marta Baranowska-Kuczko |
| author_facet | Monika Kloza Anna Krzyżewska Hanna Kozłowska Sandra Budziak Marta Baranowska-Kuczko |
| author_sort | Monika Kloza |
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| description | Empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, prevents endothelial dysfunction, but its effects on vascular tone in hypertension remain unclear. This study investigated whether EMPA modulates vasomotor tone via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) pathways in spontaneously hypertensive rats (SHR) and controls (Wistar Kyoto rats, WKY). Functional (wire myography, organ bath) and biochemical (Western blot) studies were conducted on the third-order of the superior mesenteric arteries (sMAs) and/or aortas. EMPA induced concentration-dependent relaxation of preconstricted sMAs in both groups. In SHR, EMPA enhanced acetylcholine (Ach)-induced relaxation in sMAs and aortas and reduced constriction induced by phenylephrine (Phe) and U46619 in sMAs. The SIRT1 inhibitor (EX527) abolished EMPA’s effects on Ach-mediated relaxation and U46619-induced vasoconstriction, while AMPK inhibition reduced Ach-mediated relaxation and Phe-induced vasoconstriction. SHR showed increased SGLT2 and SIRT1 expression and decreased pAMPK/AMPK levels in sMAs. In conclusion, EMPA might exert vasoprotective effects in hypertension by enhancing endothelium-dependent relaxation and reducing constriction via AMPK/SIRT1 pathways. These properties could improve vascular health in patients with hypertension and related conditions. Further studies are needed to explore new indications for SGLT2 inhibitors. |
| format | Article |
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| spelling | doaj-art-b25a66a4afa34b70a73a507f6bfdd2952025-08-20T02:15:55ZengMDPI AGCells2073-44092025-03-0114750710.3390/cells14070507Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK PathwayMonika Kloza0Anna Krzyżewska1Hanna Kozłowska2Sandra Budziak3Marta Baranowska-Kuczko4Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, 15-222 Białystok, PolandDepartment of Experimental Physiology and Pathophysiology, Medical University of Białystok, 15-222 Białystok, PolandDepartment of Experimental Physiology and Pathophysiology, Medical University of Białystok, 15-222 Białystok, PolandDepartment of Experimental Physiology and Pathophysiology, Medical University of Białystok, 15-222 Białystok, PolandDepartment of Experimental Physiology and Pathophysiology, Medical University of Białystok, 15-222 Białystok, PolandEmpagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, prevents endothelial dysfunction, but its effects on vascular tone in hypertension remain unclear. This study investigated whether EMPA modulates vasomotor tone via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) pathways in spontaneously hypertensive rats (SHR) and controls (Wistar Kyoto rats, WKY). Functional (wire myography, organ bath) and biochemical (Western blot) studies were conducted on the third-order of the superior mesenteric arteries (sMAs) and/or aortas. EMPA induced concentration-dependent relaxation of preconstricted sMAs in both groups. In SHR, EMPA enhanced acetylcholine (Ach)-induced relaxation in sMAs and aortas and reduced constriction induced by phenylephrine (Phe) and U46619 in sMAs. The SIRT1 inhibitor (EX527) abolished EMPA’s effects on Ach-mediated relaxation and U46619-induced vasoconstriction, while AMPK inhibition reduced Ach-mediated relaxation and Phe-induced vasoconstriction. SHR showed increased SGLT2 and SIRT1 expression and decreased pAMPK/AMPK levels in sMAs. In conclusion, EMPA might exert vasoprotective effects in hypertension by enhancing endothelium-dependent relaxation and reducing constriction via AMPK/SIRT1 pathways. These properties could improve vascular health in patients with hypertension and related conditions. Further studies are needed to explore new indications for SGLT2 inhibitors.https://www.mdpi.com/2073-4409/14/7/507empagliflozinSGLT2 inhibitorssirtuin 1AMPKspontaneously hypertensive ratvasoprotection |
| spellingShingle | Monika Kloza Anna Krzyżewska Hanna Kozłowska Sandra Budziak Marta Baranowska-Kuczko Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway Cells empagliflozin SGLT2 inhibitors sirtuin 1 AMPK spontaneously hypertensive rat vasoprotection |
| title | Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway |
| title_full | Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway |
| title_fullStr | Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway |
| title_full_unstemmed | Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway |
| title_short | Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway |
| title_sort | empagliflozin plays vasoprotective role in spontaneously hypertensive rats via activation of the sirt1 ampk pathway |
| topic | empagliflozin SGLT2 inhibitors sirtuin 1 AMPK spontaneously hypertensive rat vasoprotection |
| url | https://www.mdpi.com/2073-4409/14/7/507 |
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