EXPRESSION OF ALDOSTERONE SYNTHASE CYTOCHROME-P450 (P450ALDO) MESSENGER-RNA IN RAT ADRENAL GLOMERULOSA CELLS BY ANGIOTENSIN-II TYPE-1 RECEPTOR

Changes in the mRNA levels for aldosterone synthase cytochrome P450 (P 450aldo or CYP11B2) in rat adrenal glands were studied in response to angiotensin II type 1 (AT1) and type 2 (AT2) receptor antagonists. Sin ce 11 beta hydroxylase P450 (P45011 beta or CYP11B1), which shows high homology (88.5%) with P450aldo in their nucleotide sequences of the a mino acid coding regions, is also expressed in the adrenal gland, RT-P CR was performed with specific primers for each P450. Upon sodium rest riction (5 mmol Na+/kg of diet) of the rats for 14 days, the amount of the P450aldo mRNA in the adrenal glands increased 8.5 fold above from the rats fed on a normal diet (225 mmol Na+/kg of diet), whereas no s ignificant change of the P45011 beta mRNA was observed after the dieta ry sodium restriction. As shown by an immunoblot analysis, the adrenal capsule portions (mainly zona glomerulosa) of the rats kept on the lo w Na diet for 14 days expressed significantly higher level of P450aldo than those from the rats fed the normal diet. In concert with the alt eration, plasma aldosterone concentration increased. However, when a s pecific AT1 antagonist E4177 was given to the rats kept on a low Na di et, the amount and activity of P450aldo as well as the plasma aldoster one concentration was suppressed. On the other hand, the increase of P 450aldo induced by the low Na diet was not affected by an AT2-specific antagonist, PD123177.