Age-related impairment of aldosterone secretion in zona glomerulosa cells of ovariectomized rats

Background: Clinical reports have revealed impaired sodium and water balanc e in elderly persons. The present studies were designed to investigate the effects and involved mechanisms of aging on aldosterone secretion in zona g lomerulosa (ZG) cells of young and old ovariectomized (Ovx) rats, Methods: Young (3 months) and old (24 months) female rats were Ow for 4 day s before decapitation. ZG cells of young and old rats were incubated with a ngiotensin II (Ang If), tetrandrine, nifedipine, adrenocorticotropic hormon e (ACTH), forskolin, g-bromo-cyclic adenosine monophosphate (8-Br-cAMP), an d precursors at 37 degrees C for 30 minutes. Aldosterone concentrations in plasma and cell media as well as 3':5'-cAMP production in ZG cells were det ermined by radioimmunoassay, The effects of aging on the activity of aldost erone synthase and the expression of cytochrome P450 side-chain cleavage en zyme (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 th e old group than in the young group. Ang II-, ACTH-, forskolin- or 8-Br-cAM P-stimulated aldosterone secretion was attenuated in the old group as compa red with the young group. Nifedipine decreased aldosterone secretion in the young group but not in the old group. The basal and forskolin-stimulated c AMP accumulations were lower in the old than in the young group. Conclusions: These results suggest that the age-related decline in aldoster one secretion is in part a consequence of the reduced activities of biosynt hetic enzymes, adenylyl cyclase and L-type calcium channels, as well as the expression of P450scc protein in ZG cells.