Regulation of ANG II-receptor subtype and its gene expression in adrenal gland.
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 plus 3 mg.kg-1.day-1 losartan (DUP-753; i.e., DUP), low sodium (0.07%; LS), and LS plus 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) vs. 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.
Du
Y
Y
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1065, USA.
Guo
D F
DF
Inagami
T
T
Speth
R C
RC
Wang
D H
DH
D000311:Adrenal Glands / Q000502:physiology*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015870:Gene Expression; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II