Endothelial cell nitric oxide inhibits aldosterone synthesis in zona glomerulosa cells: modulation by oxygen. Am J Physiol Endocrinol Metab 2000 Oct;279(4):E846-54
Date
09/23/2000Pubmed ID
11001767DOI
10.1152/ajpendo.2000.279.4.E846Scopus ID
2-s2.0-0033712621 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
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.
Author List
Hanke CJ, Campbell WBAuthors
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinCraig J. Hanke PhD Assistant Dean, Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AldosteroneAngiotensin II
Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Endothelium, Vascular
Fibroblasts
Fluoresceins
Hydrazines
Interleukin-1
Nitrates
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Nitrites
Nitroso Compounds
Oxygen
Potassium
Zona Glomerulosa