INHIBITION OF THE EXPRESSION OF THE GENE FOR THE ANGIOTENSIN AT(1) RECEPTOR BY ANGIOTENSIN-II IN THE RAT ADRENAL-GLAND

The expression of angiotensin AT(1A) and AT(1B) receptor mRNA after co ntinuous angiotensin II administration was investigated in the rat adr enal gland. Angiotensin AT(1) receptor mRNA detected by Northern blot analysis decreased to 52.7 +/- 16.1% of control after the administrati on of angiotensin II (20 mu g/h) for 24 h, and to 70.8 +/- 8.0% after 1 week. A low dose of angiotensin II (0.2 mu g/h) also decreased angio tensin AT(1) receptor mRNA to 73.0 +/- 5.5% after 1 week. Competitive reverse transcription and polymerase chain reaction (RT-PCR) experimen ts revealed that both angiotensin AT(1A) and AT(1B) receptor mRNAs dec reased after administration of angiotensin II (20 or 0.2 mu g/h) for 1 week. Analysis of the angiotensin AT(1A) promoter by using luciferase -reporter system showed that angiotensin II (up to 1 mu M) did not hav e any effects on the promoter activity (106 +/- 5.7% after 0.1 mu M an giotensin II stimulation) in Y1 cells and cultured vascular smooth mus cle cells, although phorbol myristate acetate (PMA)decreased the promo ter activity by about 40% compared with control. These results suggest that angiotensin AT(1) receptor gene expression in the rat adrenal gl and is inhibited by angiotensin II and it may not be due to suppressio n of promoter activity. Other mechanisms such as destabilization of an giotensin AT(1) receptor mRNA or angiotensin II-induced increased bloo d pressure may be involved in the inhibition. (C) 1998 Elsevier Scienc e B.V. All rights reserved.