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Related Experiment Videos

Endothelin and cyclosporine nephrotoxicity.

V Kon1, M Awazu

  • 1Pediatric Nephrology, Vanderbilt University School of Medicine.

Renal Failure
|January 1, 1992
PubMed
Summary

Endothelin (Et) plays a key role in acute renal failure by causing vasoconstriction. Blocking Et action improves kidney function in models of acute kidney injury, highlighting its therapeutic potential.

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Area of Science:

  • Nephrology
  • Vascular Biology
  • Pharmacology

Background:

  • Persistent vasoconstriction is a hallmark of acute renal failure (ARF).
  • The precise mechanisms underlying abnormal renal vascular function in ARF remain unclear.
  • Endothelin (Et) has been implicated in ARF due to its vasoconstrictive properties and potential to increase production/gene expression.

Purpose of the Study:

  • To investigate the pathophysiologic role of endothelin in various models of acute renal failure.
  • To determine if endothelin antagonism can ameliorate renal vasoconstriction in ARF.

Main Methods:

  • Studied postischemic, endotoxin-induced, and cyclosporine (Cy)-induced nephrotoxicity models of ARF.
  • Measured circulating endothelin levels in vivo.
  • Administered endothelin antibody to antagonize Et's action.
  • Assessed renal vasoconstriction and endothelin receptor expression.

Main Results:

  • Cyclosporine and endotoxin administration elevated circulating endothelin levels in vivo.
  • Endothelin antibody treatment ameliorated renal vasoconstriction in response to renal ischemia, Cy, and endotoxin.
  • Upregulation of endothelin receptors in the kidney was observed even after circulating Et levels decreased post-cyclosporine.

Conclusions:

  • Endothelin is a significant factor in the pathophysiology of several forms of acute renal failure.
  • Antagonizing endothelin action demonstrates therapeutic potential for mitigating renal vasoconstriction in ARF.
  • Endothelin receptor modulation may also contribute to the vascular dysfunction observed in ARF.

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