title: The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.
abstract: Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.
authors.affiliation: Endocrine Research Laboratory, St. Luke's Medical Center, Milwaukee, Wisconsin 53215.
authors.forename: H
authors.initials: H
authors.lastname: Raff
authors.forename: S
authors.initials: S
authors.lastname: Kohandarvish
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D010100:Oxygen / Q000494:pharmacology*; D010313:Partial Pressure
chemical_list: D000804:Angiotensin II; D000450:Aldosterone; D003994:Bucladesine; D010100:Oxygen