Endothelial cell nitric oxide inhibits aldosterone synthesis in zona glomerulosa cells: modulation by oxygen

The regulation of aldosterone synthesis by endogenous nitric oxide (NO) was examined in cultured cells of the adrenal cortex. Endothelial NO synthase (eNOS) was detected by Western blot in cultured adrenal endothelial cells ( ECs) but not in zona glomerulosa (ZG) cells or adrenal fibroblasts. Neither inducible (iNOS) nor neuronal NOS (nNOS) isoforms were detected in the cel ls. Only ECs had NOS activity and converted [H-3]L-arginine to [H-3]L-citru lline. Angiotensin II (ANG II, 100 nM) increased EC production of nitrate/n itrite by 2.4-fold. Coincubation with ECs or treatment with DETA nonoate in creased the fluorescence of ZG cells loaded with an NO-sensitive dye, diami nofluorescein 2 diacetate (DAF-2 DA). DETA nonoate inhibited ANG II (1 nM) and potassium (10 mM)-stimulated aldosterone release in a concentration-rel ated manner. This inhibitory effect of NO was enhanced 10-fold by decreasin g the oxygen concentration from 21 to 8%. Coincubation of EC and ZG cells i n 8% oxygen inhibited ANG II-induced aldosterone release, and inhibition wa s reversed by blockade of NOS. These findings indicate that adrenal EC-deri ved NO inhibits aldosterone release by cultured ZG cells and that the sensi tivity to NO inhibition is increased at low oxygen concentrations.