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1 Department of Clinical Laboratory Medicine, 2 First Department of Internal Medicine and 3 Second Department of Physiology, Hiroshima University School of Medicine, Hiroshima, Japan 734; and 4 Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908
The cellular localization of the
AT2 receptor and the regulation of its expression in
hypertrophied left ventricle are not well known. We compared the
expression of the cardiac AT1 and AT2 receptor
in spontaneously hypertensive rats/Izumo strain (SHR/Izm) and Wistar
Kyoto rats/Izumo strain (WKY/Izm), ages 4, 12, and 20 wk, by means of
immunohistochemistry and Western blot analysis. In SHR/Izm, compared
with WKY/Izm, blood pressure (161 ± 2 vs. 120 ± 2 mmHg at 12 wk,
P
0.01, and 199 ± 3 vs. 123 ± 3 mmHg at 20 wk, P
0.01) and heart-to-body weight ratio (3.76 ± 0.07 vs. 3.06 ± 0.06 mg/g at 12 wk, P
0.01, and 3.90 ± 0.08 vs.
3.01 ± 0.12 mg/g at 20 wk, P
0.01) were
significantly elevated. There was no difference in these values between
the two strains at 4 wk of age. Histologically, 20-wk-old SHR/Izm
demonstrated myocardial hypertrophy, a thickening of the smooth muscle
layer of the intracardiac arteries, and perivascular fibrosis. By
immunohistochemistry, the AT2 receptor was localized to
cardiomyocytes and vascular endothelial cells, but not in the vascular
smooth muscle cells. No major AT2 receptor signal was
observed in perivascular fibrosis at any age in either strain of rats.
No difference was detected in this localization between the two
strains. By Western blotting, a single 44-kDa band for the
AT2 receptor and a single 60-kDa band for the
AT1 receptor were detected in ventricles from both strains
of rats at all ages. Densitometric analysis demonstrated that the
AT2 receptor 44-kDa band was decreased by 20% at 12 wk and
32% at 20 wk (P < 0.01) in SHR/Izm compared with WKY/Izm. The intensity of the AT1 receptor 60-kDa band was increased
by 57% in 20-wk-old SHR/Izm compared with WKY/Izm (P < 0.05). There was no significant difference in the intensity of
the 44- or 60-kDa bands in 4-wk-old animals of either strain. We
demonstrated a decrease in the AT2 receptor and an increase
in the AT1 receptor protein with no change in their
localizations in hypertrophied left ventricular myocytes of SHR/Izm.
immunhistochemistry; AT2 receptor; spontaneously hypertensive rats
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