Stimulation of endogenous nitric oxide production is involved in the inhibitory effect of adrenomedullin on aldosterone secretion in the rat

Adrenomedullin (AM) (10(-8) M) partially suppressed aldosterone response of dispersed rat zona glomerulosa (ZG) cells to 10 mM K+ and the nitric oxide (NO) synthase inhibitors L-NAME (10(-3) M) and 1400W (10(-4) M) effectivel y counteracted this effect of AM. The NO donor L-Arginine (L-Arg) (10(-5) M ) decreased both basal and Kt-stimulated aldosterone secretion. The guanyla te-cyclase inhibitor Ly-83583, at a concentration (10(-4) M) abolishing eit her the guanylate-cyclase activator guanylin- or L-Arg-induced cGMP release from dispersed ZG cells, did not affect the aldosterone antisecretagogue a ction of AM and L-Arg. AM (10 X M) evoked a moderate increase in cGMP relea se by dispersed ZG cells, and the effect was blocked by both 10(-4) M Ly-83 583 and 10(-3) M L-NAME. Collectively, these findings allow us (1) to confi rm that NO inhibits aldosterone secretion through a cGMP-independent mechan ism: and (2) to suggest that stimulation of endogenous NO synthesis plays a role in the mechanisms underlying the inhibitory effect of AM on Kf-stimul ated aldosterone secretion from rat ZG cells. (C) 2001 Elsevier Science Inc . All rights reserved.