Regulation of aldosterone synthase cytochrome P-450 in rat adrenals by angiotensin II and potassium.
Changes in the levels of aldosterone synthase cytochrome P-450, a recently identified enzyme in rat adrenals, were studied in response to the renin-angiotensin system and K stimuli. As examined by an immunoblot technique, the zona glomerulosa mitochondria from rats fed on a low Na-normal K diet (8.6 mmol Na+ and 207 mmol K+/kg of diet) or a low Na-high K (0.2 M KCl in drinking water) diet for 4-10 days contained significantly higher amounts of aldosterone synthase cytochrome P-450 than those from rats fed on a normal diet (86 mmol Na+ and 207 mmol K+/kg of diet). Activities of the enzyme were also found to increase by about 10-fold on day 10. In concert with these changes, both plasma renin activity and plasma aldosterone concentration increased, indicating that the renin-angiotensin system was activated in these rats. Feeding with a normal Na-high K diet also induced significantly higher levels of both amount and activity of aldosterone synthase cytochrome P-450 together with an elevated serum K concentration on day 4, though they all decreased to near the control level on the following days. On the other hand, when enalapril malate, an angiotensin I-converting enzyme inhibitor, was administered to the low Na-normal K rats, the increases in the amount and activity of the enzyme as well as in plasma aldosterone concentration were suppressed altogether. However, the enalapril administration to the low Na-high K rats suppressed the increases only partially. These results indicate that the aldosterone synthase cytochrome P-450 is an ultimate target of the regulation of aldosterone biosynthesis by angiotensin II and K.
Shibata
H
H
Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan.
Ogishima
T
T
Mitani
F
F
Suzuki
H
H
Murakami
M
M
Saruta
T
T
Ishimura
Y
Y
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004032:Diet; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000378:metabolism / Q000648:ultrastructure
D012982:Sodium, Dietary; D000804:Angiotensin II; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2; D011188:Potassium