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Effect of AT2 receptor blockade on the pathogenesis of renal fibrosis

J J Morrissey1, S Klahr

  • 1Renal Division of the Department of Internal Medicine, and the Department of Cell Biology-Physiology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.

The American Journal of Physiology
|January 14, 1999
PubMed

Insights

Blocking the AT2 receptor worsened kidney fibrosis in rats with ureteral obstruction, suggesting this receptor plays a protective role against kidney disease progression.

Area of Science:

  • Nephrology
  • Renal Pathophysiology
  • Molecular Biology

Background:

  • Tubulointerstitial fibrosis is a key factor in kidney disease progression during obstructive nephropathy.
  • Angiotensin II signaling, primarily via the AT1 receptor, is implicated in promoting kidney fibrosis.
  • The role of the Angiotensin II AT2 receptor in obstructive nephropathy remains less understood.

Purpose of the Study:

  • To investigate the specific effects of AT2 receptor antagonism on kidney injury and fibrosis in a rat model of unilateral ureteral obstruction.
  • To elucidate the contribution of the AT2 receptor to the cellular and molecular mechanisms underlying obstructive nephropathy.

Main Methods:

  • Unilateral ureteral obstruction was induced in rats.
  • Rats were treated with the AT2 receptor antagonist PD-123319.
  • Kidney tissues were analyzed for interstitial volume, collagen IV deposition, monocyte/macrophage infiltration, tubular cell apoptosis, alpha-smooth muscle actin, and p53 expression.

Main Results:

  • AT2 receptor antagonism exacerbated interstitial volume expansion and collagen IV matrix scores in the obstructed kidneys.
  • PD-123319 treatment did not alter monocyte/macrophage infiltration.
  • The AT2 receptor antagonist inhibited tubular cell apoptosis, interstitial alpha-smooth muscle actin expression, and p53 expression.

Conclusions:

  • Angiotensin II signaling through the AT2 receptor appears to exert an antifibrotic effect in the kidney during obstructive nephropathy.
  • These findings suggest a counterbalancing role for the AT2 receptor against the profibrotic actions of Angiotensin II via the AT1 receptor.
  • Targeting the AT2 receptor warrants further investigation in the context of managing obstructive kidney diseases.

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