Age-Related Impairment of Aldosterone Secretion in Zona Glomerulosa Cells of Ovariectomized Rats

Background Clinical reports have revealed impaired sodium and water balance in elderly persons. The present studies were designed to investigate the effects and involved mechanisms of aging on aldosterone secretion in zona glomerulosa (ZG) cells of young and old ovariectomized (Ovx) rats. Methods Young (3 months) and old (24 months) female rats were Ovx for 4 days before decapitation. ZG cells of young and old rats were incubated with angiotensin II (Ang II), tetrandrine, nifedipine, adrenocorticotropic hormone (ACTH), forskolin, 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP), and precursors at 37°C for 30 minutes. Aldosterone concentrations in plasma and cell media as well as 3':5'-cAMP production in ZG cells were determined by radioimmunoassay. The effects of aging on the activity of aldosterone synthase and the expression of cytochrome P450 side-chain cleavage enzyme (P450scc) in ZG cells were determined by thin-layer chromatography and Western blot analysis, respectively. Results Old rats had a lower plasma aldosterone level and a reduced basal aldosterone release from ZG cells than those in young rats. The conversions of steroidogenic precursors to aldosterone and the activity of aldosterone synthase as well as the expression of P450scc in ZG cells were lower in the old group than in the young group. Ang II-, ACTH-, forskolin- or 8-Br-cAMP-stimulated aldosterone secretion was attenuated in the old group as compared with the young group. Nifedipine decreased aldosterone secretion in the young group but not in the old group. The basal and forskolin-stimulated cAMP accumulations were lower in the old than in the young group. Conclusions These results suggest that the age-related decline in aldosterone secretion is in part a consequence of the reduced activities of biosynthetic enzymes, adenylyl cyclase and L-type calcium channels, as well as the expression of P450scc protein in ZG cells.