Attenuation of angiotensin II- and III-induced aldosterone release by prostaglandin synthesis inhibitors

W. B. Campbell, C. E. Gomez-Sanchez, B. V. Adams, J. M. Schmitz, H. D. Itskovitz

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Abstract

The effect of two prostaglandin synthesis inhibitors, indomethacin and meclofenamate, on angiotensin II (AII)- and III (AIII)-induced aldosterone release was studied in normal and sodium-depleted conscious rats and in adrenal capsular cell suspensions obtained from normal rats. In normal rats, in vivo AII and AIII were equipotent in causing dose-related increases in serum aldosterone concentrations. Indomethacin decreased the basal serum aldosterone levels by 50% and serum renin levels by 43%. In addition, the steroidogenic effects of AII and AIII were reduced by 45 and 63% with 3 mg/kg of indomethacin and 63 and 73% with 10 mg/kg, respectively. In contrast, meclofenamate failed to alter basal serum levels of aldosterone or AII-stimulated aldosterone release but inhibited serum renin levels by 27% and the aldosterone-stimulating effect of AIII by 99%. Indomethacin (3 mg/kg) and meclofenamate (2 mg/kg) inhibited urinary prostaglandin (PG)E2 and PGF2α excretion by 63 and 52% and 37 and 31%, respectively. Both inhibitors significantly decreased the adrenal capsular PGE2 and PGF2α content and the conversion of [14C]arachidonate to [14C]PGE2 and [14C]PGF2α. In sodium-depleted rats, indomethacin produced similar effects reducing the control serum aldosterone levels by 29%, AII-stimulated aldosterone by 47%, and completely suppressing the aldosterone response to AIII without altering serum renin activity. In adrenal cell suspensions, similar results were observed with indomethacin inhibiting basal and AII- and AIII-stimulated aldosterone release by 29, 81, and 93%, respectively. Meclofenamate failed to alter basal and AII-stimulated aldosterone release but inhibited that stimulated by AIII by 86%. The present findings suggest that prostaglandins modulate the effects of the renin-angiotensin system by stimulating the release of renin from the kidney and augmenting the steroidogenic effects of AII and AIII in the adrenal cortex.

Original languageEnglish (US)
Pages (from-to)1552-1557
Number of pages6
JournalJournal of Clinical Investigation
Volume64
Issue number6
DOIs
StatePublished - 1979

ASJC Scopus subject areas

  • Medicine(all)

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    Campbell, W. B., Gomez-Sanchez, C. E., Adams, B. V., Schmitz, J. M., & Itskovitz, H. D. (1979). Attenuation of angiotensin II- and III-induced aldosterone release by prostaglandin synthesis inhibitors. Journal of Clinical Investigation, 64(6), 1552-1557. https://doi.org/10.1172/JCI109615