SODIUM RESTRICTION INCREASES ALDOSTERONE BIOSYNTHESIS BY INCREASING LATE PATHWAY, BUT NOT EARLY PATHWAY, MESSENGER-RIBONUCLEIC-ACID LEVELS AND ENZYME-ACTIVITY IN NORMOTENSIVE RATS

To determine whether changes in dietary sodium intake modify the early and/or late pathways of aldosterone biosynthesis, we studied in Sprag ue-Dawley rats the effect of sodium restriction on early (conversion o f cholesterol to pregnenolone) and late (conversion of corticosterone to aldosterone) pathway activity and on the mRNA levels for the enzyme s regulating these steps. Sodium restriction increased basal and angio tensin-II-stimulated aldosterone output from isolated zona glomerulosa cells by 5- to 9-fold. This increase in aldosterone output did not ap pear to be due to changes in the conversion of cholesterol to pregneno lone or in the mRNA levels of the early pathway enzyme, cholesterol si de-chain cleavage cytochrome P-450. In contrast, sodium restriction in creased the conversion of corticosterone to aldosterone 10-fold and in creased by over 10-fold the mRNA levels of the late pathway enzyme ald osterone synthase. Sodium restriction had no effect on zona glomerulos a levels of 11beta-hydroxylase mRNA. In two other normotensive rats, D ahl salt-resistant and Wistar Kyoto, sodium restriction again specific ally increased aldosterone synthase mRNA without altering 11beta-hydro xylase 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 a n increase in aldosterone output.