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Kidney Week

Abstract: TH-PO900

Olmesartan Attenuates Kidney Injury in Experimental Alport Syndrome

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Bae, Eun Hui, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Kim, Injin, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Song, Jihong, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Ma, Seong Kwon, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Scholey, James W., University of Toronto, Toronto, Ontario, Canada
  • Kim, Soo Wan, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
Background

As angiotensin-converting enzyme 2 (ACE2) was identified as a negative regulator of the renin-angiotensin-aldosterone system, there have been many reports concerning its role in several tissues, including kidney. We have reported that ACE2 expression and activity in the kidney are reduced in experimental Alport syndrome (AS) and olmesartan has known as increased ACE2 activity.

Methods

To examine the effects of olmesartan treatment in AS, we used the Col4a3–/– mice. Mice were divided into three groups: saline-treated wild type mice group, saline-treated Col4a3–/– mice, and Ang-(1-7) treated Col4a3–/– mice group. Olmesartan medoxomil (5 mg/kg/day) was administered from 4 to 7 weeks of age via drinking water.

Results

Treatment with olmesartan led to decreased urinary NGAL excretion in 7-week-old Col4a3–/– mice. Pathological changes were attenuated by olmesartan treatment. Olmesartan ameliorated kidney fibrosis as shown by decreased expression of profibrotic genes, less accumulation of extracellular matrix proteins, and inhibition of TGF-β signaling. Further, increases in proinflammatory cytokine expression, macrophage infiltration, inflammatory signaling pathway activation, and heme oxygenase-1 (HO-1) levels in Col4a3–/– mice were also reduced by olmesartan treatment. Lastly, olmesartan influenced the turnover of renal ACE2, as it suppressed expression of TNFα-converting enzyme (TACE), a negative regulator of ACE2.

Conclusion

In summary, treatment with olmesartan alters angiotensin peptide metabolism in kidneys of Col4a3–/– mice and attenuates the progression of AS nephropathy.