From the Research Institute of Angiocardiology and Cardiovascular Clinic,
Kyushu University Faculty of Medicine, Fukuoka, Japan.
Correspondence to Toshihiro Ichiki, MD, PhD, Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University Faculty of Medicine, 3–1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Abstract—We recently reported that
administration of
N
© 1998 American Heart Association, Inc.
Scientific Contributions
Regulation of Angiotensin II Receptor Expression by Nitric Oxide in Rat Adrenal Gland
-nitro-L-arginine methyl
ester (L-NAME), an inhibitor of nitric oxide (NO)
production, activates the vascular and cardiac
renin-angiotensin systems and causes vascular thickening
and myocardial hypertrophy in rats with perivascular and
myocardial fibrosis. It has been reported that aldosterone
may contribute to the development of cardiac fibrosis, but it is not
known whether inhibition of NO synthesis affects
angiotensin II (Ang II) receptor gene expression and
aldosterone secretion. The aim of this study was to
investigate the effect of NO inhibition on the expression of Ang II
receptors in the adrenal gland and on aldosterone secretion
in rats. Wistar King A rats received normal water, L-NAME alone (1
mg/mL in the drinking water), or L-NAME and the 
1-adrenergic
receptor blocker bunazosin (0.1 mg/mL in the drinking water) for 1
week. After 1 week of treatment with L-NAME, systolic blood
pressure, plasma aldosterone concentration (PAC), and mRNA
level and number of Ang II type 1 receptor (AT1-R)
were increased. Plasma renin activity, serum
angiotensin-converting enzyme activity, and the number of
AT2-R were unchanged. Although addition of bunazosin to
L-NAME restored systolic blood pressure to the control level,
PAC and AT1-R numbers remained significantly higher than
those of control level. These results suggest that the increased
AT1-R number and PAC induced by the inhibition of NO
synthesis were independent of blood pressure and systemic
renin-angiotensin system. Therefore, hypertension and
myocardial fibrosis induced by NO blockade may be due in part to an
elevation of PAC caused by increased AT1-R in the
adrenal gland.
Key Words: nitric oxide • receptors, angiotensin • plasma aldosterone concentration • L-NAME • adrenal gland
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