title: Sodium restriction increases aldosterone biosynthesis by increasing late pathway, but not early pathway, messenger ribonucleic acid levels and enzyme activity in normotensive rats.
abstract: To determine whether changes in dietary sodium intake modify the early and/or late pathways of aldosterone biosynthesis, we studied in Sprague-Dawley rats the effect of sodium restriction on early (conversion of cholesterol to pregnenolone) and late (conversion of corticosterone to aldosterone) pathway activity and on the mRNA levels for the enzymes regulating these steps. Sodium restriction increased basal and angiotensin-II-stimulated aldosterone output from isolated zona glomerulosa cells by 5- to 9-fold. This increase in aldosterone output did not appear to be due to changes in the conversion of cholesterol to pregnenolone or in the mRNA levels of the early pathway enzyme, cholesterol side-chain cleavage cytochrome P-450. In contrast, sodium restriction increased the conversion of corticosterone to aldosterone 10-fold and increased by over 10-fold the mRNA levels of the late pathway enzyme aldosterone synthase. Sodium restriction had no effect on zona glomerulosa levels of 11 beta-hydroxylase mRNA. In two other normotensive rats, Dahl salt-resistant and Wistar Kyoto, sodium restriction again specifically increased aldosterone synthase mRNA without altering 11 beta-hydroxylase or cholesterol side-chain cleavage cytochrome P-450 mRNA levels. Thus, it appears that sodium restriction specifically increases late pathway aldosterone synthase mRNA levels, resulting in an increase in enzyme levels, followed by an increase in late pathway activity and an increase in aldosterone output.
authors.affiliation: Department of Medicine, Children's Hospital, Boston, Massachusetts.
authors.forename: G K
authors.initials: GK
authors.lastname: Adler
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: A I
authors.initials: AI
authors.lastname: Menachery
authors.forename: L M
authors.initials: LM
authors.lastname: Braley
authors.forename: G H
authors.initials: GH
authors.lastname: Williams
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D001483:Base Sequence; D002784:Cholesterol / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003345:Corticosterone / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004039:Diet, Sodium-Restricted; D008969:Molecular Sequence Data; D011284:Pregnenolone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000450:Aldosterone; D011284:Pregnenolone; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013250:Steroid Hydroxylases; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003345:Corticosterone