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Inhibition of aldosterone release by hypoxia in vitro: interaction with carbon monoxide. J Appl Physiol (1985) 1994 Feb;76(2):689-93

Date

02/01/1994

Pubmed ID

8175579

DOI

10.1152/jappl.1994.76.2.689

Scopus ID

2-s2.0-0028211791   5 Citations

Abstract

We have demonstrated that the aldosteronogenic pathway of the zona glomerulosa is unusually sensitive to modest changes in PO2 (Michaelis constant for O2 approximately 95 Torr). The current study evaluated the interaction of CO (the classic ligand for P-450 enzymes) and the decreases in O2 on aldosteronogenesis in vitro. Bovine adrenocortical zona glomerulosa cells were incubated for 2 h and stimulated with either adenosine 3',5'-cyclic monophosphate (cAMP) or angiotensin II. Ten and 20% CO led to significant decreases in cAMP- and angiotensin II-stimulated aldosteronogenesis. The combination of 20% CO and moderate decreases in PO2 (from approximately 140 to approximately 100 Torr) led to an interactive decrease in aldosterone production. The conversion of corticosterone to aldosterone catalyzed by aldosterone synthase, which is the site of O2 sensitivity, was not significantly inhibited by CO. We conclude that the aldosterone pathway is not exceptionally sensitive to CO compared with other steroidogenic pathways. This observation suggests that the unique O2-sensitive properties of the aldosterone pathway located primarily within aldosterone synthase may not reside in its CO binding site (i.e., heme).

Author List

Raff H, Jankowski B

Author

Hershel Raff PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aldosterone
Angiotensin II
Animals
Carbon Monoxide
Cattle
Cells, Cultured
Corticosterone
Cyclic AMP
Female
Hypoxia
Mineralocorticoid Receptor Antagonists
Oxygen
Zona Glomerulosa
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d