Nitric oxide inhibits human aldosteronogenesis without guanylyl cyclase stimulation.

Deta nonoate (deta-NO), a zwitterion nitric oxide (NO) donor, potently inhibited forskolin- and angiotensin II-stimulated aldosterone production in human adrenocortical H295R cells in a concentration-dependent manner (0.1-1000 microM). The half-maximal and maximal inhibition of forskolin-evoked aldosteronogenesis occurred at 0.6 and 100 microM deta-NO, respectively. The respective half-maximal and maximal deta-NO-mediated inhibition of angiotensin II-stimulated aldosterone generation occurred at 150 microM and 1 mM. In H295R cells, deta-NO and sodium nitroprusside did not stimulate cGMP production, and the soluble guanylyl cyclase inhibitor oxadiazoloquinoxalinone (10 microM) did not block deta-NO-mediated attenuation of aldosteronogenesis. 25-Hydroxycholesterol (10 microM)-facilitated aldosterone synthesis was also diminished with half-maximal and maximal inhibition occurring at 120 microM and 1 mM deta-NO, respectively. Taken together, these results demonstrate that NO inhibits human aldosteronogenesis without stimulating guanylyl cyclase in H295R cells.