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Abstract: PO2149

Inhibition of Mineralocorticoid Receptor Ameliorates Salt-Sensitive Hypertension After Ischemic-Reperfusion Injury in Rats

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Matsumoto, Takumi, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
  • Doi, Shigehiro, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
  • Nakashima, Ayumu, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
  • Masaki, Takao, Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan
Background

The transition from acute kidney injury (AKI) to chronic kidney diseases a major pathway for progression to end-stage kidney disease. Although hypertension is reported to be associated with the clinical progression of chronic kidney disease, the mechanism by which AKI induces hypertension remains elusive. Previous studies have demonstrated that salt-sensitive hypertension occurs in rats after ischemic reperfusion injury (IRI), a rodent model of AKI, and that distal nephrons play an important role in the development of salt-sensitive hypertension. Herein, we investigated the role of the mineral corticoid receptor (MR) in the progression of IRI-induced salt-sensitive hypertension in rats.

Methods

Seven days after right nephrectomy, IRI was induced by clamping of the left renal artery for 45 min in 8-week-old male Sprague-Dawley rats. Rats were sacrificed at 7 days after IRI, and expression of MR examined. IRI rats were also given drinking water with 1% sodium chloride (IRI/NaCl), or were implanted with an osmotic mini-pump to infuse aldosterone (IRI/Aldo). Esaxerenone (3 mg/kg/day; a non-steroidal MR antagonist [MRA]), or vehicle were administrated in IRI/NaCl and IRI/Aldo rats for 6 weeks. Blood pressure and urinary protein level were measured weekly during the study period. Protein expression in renal tissues was examined by immunoblotting and/or immunohistochemistry.

Results

MR expression was increased at 7 days after IRI. Further, blood pressure and urinary protein excretion increased in IRI/NaCl and IRI/Aldo rats over the 6-week observation period, whereas these effects were negated by MRA administration. Similarly, MRA ameliorated the expression of the β-epithelial sodium channel (ENaC), γ-ENaC, and fibrotic markers, but not α-ENaC or NaCl cotransporter channel in both IRI/NaCl and IRI/Aldo rats.

Conclusion

Upregulation of MR, β-ENaC, and γ-ENaC may play a pivotal role in the development of salt-sensitive hypertension in rats after IRI.

Funding

  • Government Support - Non-U.S.