2023 Fiscal Year Final Research Report
Interaction between sympathetic nervous system and sodium-glucose cotransporter 2 in heart failure
| Project/Area Number |
21K16094
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | sympathetic nerve / renal afferent / renal denervation / heart failure / SGLT2 |
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| Outline of Final Research Achievements |
In rats with heart failure induced by coronary artery ligation, compared with normal rats, (1) heart weight and left ventricular end-diastolic pressure increased and left ventricular ± dP/dt decreased. (2) Total renal nerve activity and afferent renal nerve activity increased accompanied with increased norepinephrine content in the renal cortex. (3) SGLT2 expressions in the renal proximal tubules were increased. Consistent with this finding, the diuretic response to intravenous dapagliflozin, an SGLT2 inhibitor, were increased. (4) Renal denervation normalised SGLT2 expressions and response to dapagliflozin in rats with heart failure. These results suggest that SGLT2 and renal nerves contribute to fluid regulation through a bidirectional linkage, and that their dysfunction exacerbates heart failure.
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| Free Research Field |
Autonomic cardiology
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は臨床試験で示されているSGLT2阻害薬の心不全改善や心血管イベント抑制のメカニズムの一部である可能性があり、SGLT2阻害薬の心不全治療薬としての使用や心血管イベントの一次予防と二次予防の使用に科学的根拠を与えるものである。また、交感神経活性化を背景に有する病態に対する、SGLT2阻害薬や腎デナベーションの病態改善効果を示すものであり、実臨床における心血管代謝疾患および関連疾患を対象とした自律神経修飾治療による介入への発展・応用基盤となる点において意義がある。
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