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Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
The present study was designed to
determine whether nonhypertensive elevations of plasma ANG II would
modify the expression of genes involved in renal injury that could
influence oxidative stress and extracellular matrix formation in the
renal medulla using microarray, Northern, and Western blot techniques.
Sprague-Dawley rats were infused intravenously with either ANG II (5 ng · kg
1 · min
1)
or vehicle for 7 days (n = 6/group). Mean arterial
pressure averaged 110 ± 0.6 mmHg during the control period and
113 ± 0.4 mmHg after ANG II. The mRNA of 1,751 genes (~80% of
all currently known rat genes) that was differentially expressed (ANG
II vs. saline) in renal outer and inner medulla was determined. The
results of 12 hybridizations indicated that in response to ANG II, 11 genes were upregulated and 25 were downregulated in the outer medulla,
while 11 were upregulated and 13 were downregulated in the inner
medulla. These differentially expressed genes, most of which were not
known previously to be affected by ANG II in the renal medulla, were
found to group into eight physiological pathways known to influence
renal injury and kidney function. Particularly, expression of several
genes would be expected to increase oxidative stress and interstitial
fibrosis in the outer medulla. Western blot analyses confirmed
increased expression of transforming growth factor-
1 and collagen
type IV proteins in the outer medulla. Results demonstrate that
nonhypertensive elevations of plasma ANG II can significantly alter the
expression of a variety of genes in the renal outer medulla and
suggested the vulnerability of the renal outer medulla to the injurious effect of ANG II.
renal inner medulla; cDNA microarray
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