Oxygen sensitivity of potassium- and angiotensin II-stimulated aldosterone release by bovine adrenal cells.
Angiotensin II (AII) and extracellular K+, acting through different intracellular mechanisms, stimulate aldosterone release in a synergistic fashion. We have previously shown that decreases in oxygen (O2) within the physiological range inhibit AII, cyclic AMP (cAMP) and ACTH-stimulated aldosterone release. The present experiment evaluated the effect of various concentrations of O2 on K+-stimulated aldosterone release in the presence and absence of AII. Dispersed bovine adrenal glomerulosa cells were incubated with different concentrations of K+ (0.9-5.4 mmol/l) without and with AII (10 nmol/l) under different concentrations of O2 (0, 5 or 50%); 21% O2 (pO2 = 19.9 +/- 0.5 kPa,n = 9) was used as reference control for comparison. In all cases, increases in K+ stimulated aldosterone release, an effect augmented by AII. Under 0% O2 (pO2 = 8.1 +/- 0.3 kPa, n = 3) and 5% O2 (pO2 = 12.8 +/- 0.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly inhibited compared with that under 21% O2. Conversely, under 50% O2 (pO2 = 36.3 +/- 2.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly augmented. Cortisol secretion was not significantly affected by 5% or 50% O2 but was significantly decreased under 0% O2. The effect of O2 on K+/AII stimulation of aldosterone release, as well as previous experiments with cAMP, progesterone and ACTH, suggest a final common post-receptor oxygen-sensitive component of the aldosterone synthetic pathway. It is suggested that one or more enzymes in the aldosterone synthetic pathway is/are exquisitely sensitive to small changes in O2 within the physiological range.
Brickner
R C
RC
Endocrine Research Laboratory, St Luke's Medical Center, Milwaukee, Wisconsin 53215.
Raff
H
H
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D013268:Stimulation, Chemical
D000804:Angiotensin II; D000450:Aldosterone; D011188:Potassium; D010100:Oxygen