Regulation of renal growth factors and clusterin by angiotensin at1
receptors during neonatal ureteral obstruction.
Chung, Ky Hyun, R. Ariel Gomez, Robert L. Chevalier.
Department of Urology, Gyeong-sang National University, Chinju, Korea,
Department of Pediatrics, University of Virginia, School of Medicine,
Charlottesville, Virginia
APStracts 2:0001F, 1995.
Unilateral ureteral obstruction (UUO) in the neonate impairs growth of the
ipsilateral kidney. Since renal renin expression is increased by UUO, we
hypothesized that by activation of AT1 receptors, angiotensin II (ANG II)
regulates expression of transforming growth factor-beta 1 (TGF-[beta]1) and
epidermal growth factor (EGF) in the obstructed kidney. Sprague-Dawley rats
underwent left UUO or sham operation within the first 48 h of life, and
received losartan, 40 mg/kg/d, or saline. After 14 days, steady-state renal
mRNA was determined for renin, TGF-[beta]1, EGF, and clusterin. Losartan
reduced the DNA content of the intact kidneys, but did not further decrease
that of the obstructed kidney. Losartan increased renal renin expression and
decreased EGF expression 80% regardless of UUO. In contrast, losartan reduced
TGF-[beta]1 expression by 34% in obstructed kidneys, but did not affect TGF-
[beta]1 in intact kidneys. Losartan increased clusterin expression by 60% in
obstructed kidneys and 7-fold in intact kidneys. We conclude that activation
of the ANG II AT1 receptor is necessary for normal renal growth, and that TGF-
[beta]1 is regulated by AT1 receptors in the obstructed, but not intact
kidneys. Through AT1 receptors, endogenous ANG II stimulates EGF and inhibits
clusterin expression.
Received 11 October 1994; accepted in final form 4 January 1995.
APS Manuscript Number F359-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.