H. Raff et B. Jankowski, INHIBITION OF ALDOSTERONE RELEASE BY HYPOXIA IN-VITRO - INTERACTION WITH CARBON-MONOXIDE, Journal of applied physiology, 76(2), 1994, pp. 689-693
We have demonstrated that the aldosteronogenic pathway of the zona glo
merulosa is unusually sensitive to modest changes in PO2 (Michaelis co
nstant for O-2 approximate to 95 Torr). The current study evaluated th
e interaction of CO (the classic ligand for P-450 enzymes) and the dec
reases in O-2 on aldosteronogenesis in vitro. Bovine adrenocortical zo
na glomerulosa cells were incubated for 2 h and stimulated with either
adenosine 3',5'-cyclic monophosphate (cAMP) or angiotensin II. Ten an
d 20% CO led to significant decreases in cAMP- and angiotensin II-stim
ulated aldosteronogenesis. The combination of 20% CO and moderate decr
eases in PO2 (from similar to 140 to similar to 100 Torr) led to an in
teractive decrease in aldosterone production. The conversion of cortic
osterone to aldosterone catalyzed by aldosterone synthase, which is th
e site of O-2 sensitivity, was not significantly inhibited by CO. We c
onclude that the aldosterone pathway is not exceptionally sensitive to
CO compared with other steroidogenic pathways. This observation sugge
sts that the unique O-2-sensitive properties of the aldosterone pathwa
y located primarily within aldosterone synthase may not reside in its
CO binding site (i.e., heme).