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Eplerenone improves hyperglycemia and sympathetic excitation in chronic renocardiac syndrome in rats

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Abstract

We aimed to assess the efficacy of eplerenone, a steroidal mineralocorticoid receptor antagonist known to reduce blood pressure and mitigate cardiovascular disease (CVD) progression, in retarding the progression of chronic kidney disease (CKD) and CVD in a rat model of type 4 cardiorenal syndrome (CRS). We grouped rats into four experimental categories: sham surgery, sham treatment with eplerenone, nephrectomy without eplerenone (Nx), and nephrectomy with eplerenone (Nx + EP). For the Nx + EP group, rats received five-sixths nephrectomy, inducing CKD and CVD conditions such as renal hypertension and hyperglycemia, and were then treated with eplerenone (100 mg/kg/day, orally) over 4 weeks after an initial 4-week observation period. Heart rate, blood pressure, blood sugar levels, and sympathetic nerve excitation were monitored biweekly. In addition, assessments of renal and cardiac tissues, including evaluation of renal tubulointerstitial injury, glomerular injury, and cardiomyocyte hypertrophy, were conducted at week 8. Eplerenone administration mitigated CKD and CVD progression in the Nx + EP group, evident by improved blood pressure (217.3 ± 5.4 versus 175.3 ± 5.6), blood sugar (121.8 ± 1.3 versus 145.6 ± 6.0) level, reduced sympathetic nerve excitation, and cardiomyocyte hypertrophy compared to the Nx group. However, renal tubulointerstitial injury, glomerular injury, and cardiovascular dysfunction, which were increased in rats with type 4 CRS, did not show significant changes with eplerenone treatment. Our study demonstrated that eplerenone treatment did not exacerbate type 4 CRS but improved blood pressure, blood sugar levels, sympathetic nerve excitation, and cardiomyocyte hypertrophy in this model.

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Acknowledgements

We are grateful to Tzu-Jiun Kuo and Kuan-Hung Lin for their technical assistance and invaluable input for this manuscript.

Funding

This work was supported by the Kaohsiung Veterans General Hospital (KSVGH110-150 and KSVGH111-152); the Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST111-G3-2–2 and VGHUST112-G3-2–3), and the Zouying Branch of Kaohsiung Armed Forces General Hospital (ZBH 108–31), and the Ministry of Science and Technology of Taiwan (MOST 110–2320-B-075B-001-MY3).

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Author notes

  1. Chieh-Jen Wu and Yu-He Li contributed equally to this work.

Authors and Affiliations

  1. Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 813414, Taiwan

    Chieh-Jen Wu

  2. Department of Laboratory Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, 813204, Taiwan

    Yu-He Li

  3. Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, 813414, Taiwan

    Fu-Zong Wu

  4. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, 813414, Taiwan

    Hsin-Hung Chen

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  1. Chieh-Jen Wu
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Contributions

All authors contributed to the conception and design of the study. Chieh-Jen Wu and Yu-He Li carried out material preparation, data collection, and analysis, while Fu-Zong Wu was responsible for data verification. The initial draft of the manuscript was authored by Hsin-Hung Chen, who also performed revisions and supervised the entire study. All authors provided feedback on subsequent versions of the manuscript and read and approved the final version.

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Correspondence to Hsin-Hung Chen.

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All animal research protocols were approved by the Research Animal Facility Committee of the Kaohsiung Veterans General Hospital (VGHKS 2021–2023-A037-110).

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Wu, CJ., Li, YH., Wu, FZ. et al. Eplerenone improves hyperglycemia and sympathetic excitation in chronic renocardiac syndrome in rats. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1081–1092 (2024). https://doi.org/10.1007/s00210-023-02665-5

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