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

Abstract

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 cells. Only ECs had NOS activity and converted [(3)H]L-arginine to [(3)H]L-citrulline. Angiotensin II (ANG II, 100 nM) increased EC production of nitrate/nitrite by 2.4-fold. Coincubation with ECs or treatment with DETA nonoate increased the fluorescence of ZG cells loaded with an NO-sensitive dye, diaminofluorescein 2 diacetate (DAF-2 DA). DETA nonoate inhibited ANG II (1 nM) and potassium (10 mM) -stimulated aldosterone release in a concentration-related manner. This inhibitory effect of NO was enhanced >10-fold by decreasing the oxygen concentration from 21 to 8%. Coincubation of EC and ZG cells in 8% oxygen inhibited ANG II-induced aldosterone release, and inhibition was reversed by blockade of NOS. These findings indicate that adrenal EC-derived NO inhibits aldosterone release by cultured ZG cells and that the sensitivity to NO inhibition is increased at low oxygen concentrations.

Endothelium-Derived Steroidogenic Factor Enhances Angiotensin II-Stimulated Aldosterone Release by Bovine Zona Glomerulosa Cells

“…ECs also release factors capable of inhibiting aldosterone release during conditioning. Endothelial nitric oxide release will inhibit ZG cell aldosterone release (22,26). However, the short half-life of the nitric oxide in buffer makes it an unlikely inhibitory factor in CM (26).…”

Angiotensin II Relaxations of Bovine Adrenal Cortical Arteries

“…21 Conversely, factors originating from the adrenal vasculature influence adrenal steroidogenesis. Endothelial cell NO inhibits aldosterone secretion, 30 whereas an endothelium-derived peptide stimulates aldosterone production. 31 The results from the current study suggest that vascular Ang II metabolism could influence the level of Ang II-dependent regulation of vascular tone and modulate the concentrations of Ang II available for the stimulation of steroidogenesis.…”

Chronic administration of nitric oxide reduces angiotensin II receptor type 1 expression and aldosterone synthesis in zona glomerulosa cells

“…It is not known whether NO affects the expression and localization of ANG II receptors in ZG cells. We (9,10) previously showed that acute treatment with NO inhibited the ANG II-, 25-hydroxycholesterol-, and pregnenolone-stimulated aldosterone synthesis in ZG cells, and this mechanism is guanylyl cyclase/cGMP independent. NO inhibited aldosterone biosynthesis by binding steroidogenic enzymes.…”

“…NO inhibited aldosterone biosynthesis by binding steroidogenic enzymes. The sensitivity to NO inhibition was increased at low oxygen concentrations (9). These observations led us to examine the effects of chronic exposure of ZG cells to NO on the expression of AT1 receptors and aldosterone synthesis.…”