Regulation of ANG II-receptor subtype and its gene expression in adrenal gland

We have previously demonstrated that two isoforms (AT(1A) and AT(1B)) Of the angiotensin II (ANG II) type 1 (AT(1)) 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 AT(1A) and AT(1B) gene expression in the adrenal gland by activating the AT(1) 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 AT(1A): 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 AT(1B):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 AT(1) 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 AT(1A) and AT(1B) gene expression and elevates the AT(1) receptor density in the adrenal gland. Blockade of the binding of ANG II to the AT(1) receptor by losartan prevents the increases in AT(1A) and AT(1B) mRNA expression and the AT(1) receptor density induced by sodium depletion, suggesting that these changes in the adrenal gland are mediated by activation of the AT(1) receptor. These results will provide a basis for future experiments to further elucidate transcriptional regulation or functional activity of each of the receptor subtypes.