title: Effect of CO2/pH on the aldosterone response to hypoxia in bovine adrenal cells in vitro.
abstract: Acidosis increases and hypoxia decreases aldosterone production from the adrenal zona glomulerosa in vivo, in situ, and in vitro. These effects appear to be located at different steps in the steroidogenic process. Because respiratory acidosis and hypoxemia are common sequelae of chronic lung disease, the present experiments evaluated the interaction of hypoxia and CO2 (with uncompensated or compensated extracellular pH) on aldosteronogenesis in vitro. Bovine adrenal zona glomerulosa cells were stimulated with angiotensin II (ANG II) or adenosine 3',5'-cyclic monophosphate under room air control (21% O2-0% CO2), CO2 per se (21% O2-10% CO2), hypoxia per se (10% O2-0% CO2), and the combination of CO2 and hypoxia (10% O2-10% CO2). Furthermore, under CO2, pH was either allowed to decrease from 7.2 to 6.8 (uncompensated) or its decrease was minimized (> 7.05) with NaOH (compensated). CO2 without pH compensation led to a significant increase in ANG II-stimulated aldosterone release; when the decrease in pH was minimized, CO2 inhibited ANG II-stimulated aldosterone release. Hypoxia inhibited aldosterone release; the inhibitory effect of hypoxia predominated when combined with CO2. In the presence of cyanoketone, pregnenolone production from endogenous precursors (early pathway) was unaffected. However, the conversion of corticosterone to aldosterone (late pathway) was inhibited by low O2 but unaffected by CO2. It is concluded that the inhibitory effect of low O2 on the late pathway predominates over the effects of uncompensated or compensated simulated respiratory acidosis on aldosteronogenesis.
authors.affiliation: Endocrine Research Laboratory, St. Luke's Medical Center, Milwaukee 53215.
authors.forename: H
authors.initials: H
authors.lastname: Raff
authors.forename: B
authors.initials: B
authors.lastname: Jankowski
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism* / Q000473:pathology; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology*; D002417:Cattle; D003345:Corticosterone / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D011284:Pregnenolone / Q000096:biosynthesis
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D002245:Carbon Dioxide; D000450:Aldosterone; D003994:Bucladesine; D011284:Pregnenolone; D010100:Oxygen; D003345:Corticosterone