The effect of at2 receptor blockade on the pathogenesis of renal
fibrosis.
Morrissey, Jeremiah J., and Saulo Klahr.
Renal Division and the Department of Internal Medicine, Washington
University School of Medicine and Barnes-Jewish Hospital, St. Louis,
Missouri 63110
APStracts 5:0170F, 1998.
Cellular and molecular events contributing to tubulointerstitial
fibrosis of the kidney during obstructive nephropathy are driven in
large part through increased angiotensin II levels in the obstructed
kidney. Angiotensin converting enzyme inhibition or AT1 receptor
antagonism have been shown to ameliorate the fibrosis of the kidney
due to obstruction of the ureter. In this investigation, we determine
the effects of the AT2 receptor antagonist PD123319 on
pathophysiologic events within the kidneys of rats with unilateral
ureteral obstruction. Treatment with PD123319 was found to exacerbate
the increase in interstitial volume and collagen IV matrix score of
the ureteral obstructed kidney. Monocyte/macrophage infiltration of
the injured kidney was no different between treated and untreated
animals. The AT2 receptor antagonist did, however, inhibit apoptosis
of tubular cells, (-smooth muscle actin expression within the
interstitium, and p53 expression in the ureteral obstructed kidney.
These results suggest that angiotensin II operating through the AT2
receptor exerts an antifibrotic effect on the kidney during
obstructive nephropathy in opposition to the profibrotic effects of
angiotensin II operating through the AT1 receptor.
Received 23 May 1998; accepted in final form 17 September 1998.
APS Manuscript Number F70-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 20 October 1998