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

H. Raff, B. Jankowski, W. C. Engeland, M. K. Oaks, P. E. Papanek

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

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