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Empagliflozin Induces Vascular Relaxation in Rat Coronary Artery Due to Activation of BK Channels.
Kong, Qi; Qian, Ling-Ling; Zhang, Lei; Liu, Huan-Huan; Yang, Fan; Zhang, Xiao-Lu; Wang, Chao; Zhao, Xiao-Xi; Li, Ku-Lin; Wang, Ru-Xing.
Afiliación
  • Kong Q; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Qian LL; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Zhang L; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Liu HH; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Yang F; Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, People's Republic of China.
  • Zhang XL; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Wang C; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Zhao XX; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Li KL; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
  • Wang RX; Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People's Republic of China.
Diabetes Metab Syndr Obes ; 17: 247-257, 2024.
Article en En | MEDLINE | ID: mdl-38269338
ABSTRACT

Purpose:

The aim of this study was to investigate the effects and mechanisms of SGLT2 inhibitor empagliflozin on diabetic coronary function.

Methods:

A rat diabetic model was established by injection of streptozotocin. Rats in the treated group were administered empagliflozin by gavage and rat coronary vascular tensions were measured after eight weeks. Large conductance calcium activated K+ channel currents were recorded using a patch clamp technique, while human coronary artery smooth muscle cells were used to explore the underlying mechanisms.

Results:

After incubation with empagliflozin (10, 30, 100, 300, 1000 µmol/L), the Δ relaxation % of rat coronary arteries were 2.459 ± 1.304, 3.251 ± 1.119, 6.946 ± 3.407, 28.36 ± 11.47, 86.90 ± 3.868, respectively. Without and with empagliflozin in the bath solution, BK channel opening probabilities at a membrane potential of +60 mV were 0.0458 ± 0.0517 and 0.3413 ± 0.2047, respectively (p < 0.05, n = 4 cells). After incubation with iberiotoxin, the Δ tensions of rat coronary arteries in the control (Ctrl), untreated (DM), low empagliflozin (10 mg/kg/d)-treated (DM+L-EMPA) and high empagliflozin (30mg/kg/d)-treated (DM+H-EMPA) group were 103.20 ± 5.85, 40.37 ± 22.12, 99.47 ± 28.51, 78.06 ± 40.98, respectively (p < 0.01 vs Ctrl, n = 3-7; p < 0.001 vs DM+L-EMPA, n = 5-7). Empagliflozin restored high glucose-induced downregulation of Sirt1, Nrf2, and BK-ß1, while the effect of empagliflozin disappeared in the presence of EX-527, a Sirt1 selective inhibitor.

Conclusion:

Empagliflozin has a vasodilation effect on the coronary arteries in a concentration-dependent manner and can activate BK channels via the Sirt1-Nrf2 mechanism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Diabetes Metab Syndr Obes Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Diabetes Metab Syndr Obes Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda