EFFECT OF CO2 PH ON THE ALDOSTERONE RESPONSE TO HYPOXIA IN BOVINE ADRENAL-CELLS IN-VITRO/

Acidosis increases and hypoxia decreases aldosterone production from t he adrenal zona glomulerosa in vivo, in situ, and in vitro. These effe cts appear to be located at different steps in the steroidogenic proce ss. Because respiratory acidosis and hypoxemia are common sequelae of chronic lung disease, the present experiments evaluated the interactio n of hypoxia and CO2 (with uncompensated or compensated extracellular pH) on aldosteronogenesis in vitro. Bovine adrenal zona glomerulosa ce lls were stimulated with angiotensin II (ANG II) or adenosine 3',5'-cy clic 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 ei ther allowed to decrease from 7.2 to 6.8 (uncompensated) or its decrea se was minimized (>7.05) with NaOH (compensated). CO2 without pH compe nsation 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 endogeno us precursors (early pathway) was unaffected. However, the conversion of corticosterone to aldosterone (late pathway) was inhibited by low O 2 but unaffected by CO2. It is concluded that the inhibitory effect of low O2 on the late pathway predominates over the effects of uncompens ated or compensated simulated respiratory acidosis on aldosteronogenes is.