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

Abstract

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) effectively counteracted this effect of AM. The NO donor L-Arginine (L-Arg) (10 −5 M) decreased both basal and K +-stimulated aldosterone secretion. The guanylate-cyclase inhibitor Ly-83583, at a concentration (10 −4 M) abolishing either the guanylate-cyclase activator guanylin- or L-Arg-induced cGMP release from dispersed ZG cells, did not affect the aldosterone antisecretagogue action of AM and L-Arg. AM (10 −8 M) evoked a moderate increase in cGMP release by dispersed ZG cells, and the effect was blocked by both 10 −4 M Ly-83583 and 10 −3 M L-NAME. Collectively, these findings allow us (1) to confirm that NO inhibits aldosterone secretion through a cGMP-independent mechanism; and (2) to suggest that stimulation of endogenous NO synthesis plays a role in the mechanisms underlying the inhibitory effect of AM on K +-stimulated aldosterone secretion from rat ZG cells.