Regulation of angiotensin ii receptor subtype and its gene
expression in adrenal gland: role of type 1 angiotensin ii
receptor.
Du, Yong, Deng-Fu Guo, Tadashi Inagami, Robert C. Speth, Donna H.
Wang.
Department of Internal Medicine, Hypertension and Vascular Research
Laboratories, University of Texas Medical Branch, Galveston, TX
77555-1065, and, Department of Biochemistry, Vanderbilt University
School of Medicine, Nashville, TN and Department of Veterinary and
Comparative Anatomy, Pharmacology and Physiology, Washington State
University, Pullman, WA
APStracts 3:0037H, 1996.
We have previously demonstrated that two isoforms (AT1A and AT1B) of
the angiotensin II (Ang II) type 1 (AT1) receptor exist in the rat
kidney and are differentially regulated by a low sodium diet. The
present experiment was designed to test the hypothesis that sodium
deficiency upregulates AT1A and AT1B gene expression in the adrenal
gland by activating the AT1 receptor. Wistar rats (7 wk old) were
divided into four groups (n=10 each) and fed: normal sodium (0.5%,
NS), NS + 3mg/kg/day losartan (DUP), low sodium (0.07%, LS) and LS +
DUP. After 2 wks, body weight and mean arterial pressure were not
different (p>0.05). Northern blot analysis showed that the ratio
of AT1A : glyceraldehyde 3 phosphate dehydrogenase (GAPDH) mRNA in
the adrenal gland was increased (p<0.001) by 172% in LS, but was
unchanged in NS+DUP and LS+DUP vs NS. The ratio of adrenal AT1B:GAPDH
mRNA was increased (p<0.001) by 245% in LS, and unchanged in
NS+DUP and LS+DUP vs NS. Radioligand binding indicated that AT1
receptors (fmol/mg protein) in the adrenal gland were increased in LS
(141+/-17, p<0.001) versus NS (54+/-3), NS+DUP (43+/-5) and
LS+DUP (56+/-6). We conclude that sodium deficiency increases both
AT1A and AT1B gene expression and elevates the AT1 receptor density
in the adrenal gland. Blockade of the binding of Ang II to the AT1
receptor by losartan prevents the increases in AT1A and AT1B mRNA
expression and the AT1 receptor density induced by sodium depletion,
suggesting that these changes in the adrenal gland are mediated by
activation of the AT1 receptor. These results will provide a basis
for future experiments to further elucidate transcriptional
regulation or functional activity of each of the receptor subtypes.
Received 4 October 1995; accepted in final form 5 January 1996.
APS Manuscript Number H938-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96