Faculty Collaboration Database

Attenuation of angiotensin II- and III-induced aldosterone release by prostaglandin synthesis inhibitors. J Clin Invest 1979 Dec;64(6):1552-7

Date

12/01/1979

Pubmed ID

500824

Pubmed Central ID

PMC371307

DOI

10.1172/JCI109615

Scopus ID

2-s2.0-0018603978 (requires institutional sign-in at Scopus site)   52 Citations

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)E(2) and PGF(2alpha) excretion by 63 and 52% and 37 and 31%, respectively. Both inhibitors significantly decreased the adrenal capsular PGE(2) and PGF(2alpha) content and the conversion of [(14)C]arachidonate to [(14)C]PGE(2) and [(14)C]PGF(2alpha). 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.

Author List

Campbell WB, Gomez-Sanchez CE, Adams BV, Schmitz JM, Itskovitz HD

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenal Cortex
Aldosterone
Angiotensin II
Angiotensin III
Animals
Cells, Cultured
Indomethacin
Male
Meclofenamic Acid
Prostaglandins E
Prostaglandins F
Rats
Renin
ortho-Aminobenzoates