Attenuation of angiotensin II- and III-induced aldosterone release by prostaglandin synthesis inhibitors.
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.
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D000805:Angiotensin III / Q000037:antagonists & inhibitors*; D000818:Animals; D002478:Cells, Cultured; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D011458:Prostaglandins E / Q000652:urine; D011460:Prostaglandins F / Q000652:urine; D051381:Rats; D012083:Renin / Q000097:blood; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D011458:Prostaglandins E; D011460:Prostaglandins F; D062367:ortho-Aminobenzoates; D000804:Angiotensin II; D000805:Angiotensin III; D008469:Meclofenamic Acid; D000450:Aldosterone; D012083:Renin; D007213:Indomethacin