Hypoxia in vivo inhibits the expression of aldosterone synthase (p450aldo) mrna levels in the rat adrenal cortex

Hypoxia in vivo leads to a dissociation of the renin-angiotensin aldosterone system such that aldosterone synthesis decreases without a decrease in renin. The present study determined whether this could be do lu hypoxia-induced inhibition of the expression of the cytochrome P450 enzyme unique to the aldosterone pathway (P450aldo). Rats were exposed to nonnoxia (3/experiment) or hypoxia (FIO₂ = 0.10; 3/experiment) for 3 days after which the adrenal glands were removed and analyzed for steroidogenic enzyme mRNA in vitro by reverse transcription-competitive polymerase chain reaction and in situ hy hybridization histochemistry. Exposure to hypoxia in vivo resulted in a 4-fold inhibition of steady state P450aldo mRNA levels. However, hypoxia had no significant effect on l lβ-hydroxylase or side chain cleavage mRNA levels. We conclude that exposure to hypoxia in vivo results in a specific inhibition of aldosterone synthesis by decreasing the expression of P450aldo, the steroidogenic cytochrome P450 enzyme unique to aldosteronogenesis. Possible mechanisms include increased ACTH and/or a direct regulation of P450aldo gene transcription hy oxygen. (Support: AHA/Wisconsin Grant-in-Aid and NIH GM50I50).