Stimulation of renin release by PGE2 and PGI2 infusion in the dog: enhancing effect of ureteral occlusion or administration of ethacrynic acid

Abstract

This study on 19 anaesthetized dogs had two objectives. The first was to compare the potencies of PGE2 and PGI2 as stimulators of renin release and demonstrate their dependency on activation of intrarenal mechanisms for renin release. The second objective was to demonstrate that ethacrynic acid (ECA) increases renin release not as a stimulator, but by activating intrarenal mechanisms. After inhibiting renal prostaglandin synthesis by indomethacin, PGE2 and PGI2 infused into the aorta proximal to the renal arteries exerted no significant effects on renin release, but increased renin release during ureteral occlusion. At equimolar infusion rates, PGI2 increased renin release twice as much as PGE2, but this difference in potency may reflect differences in degradation since 86% of PGE2 and 29% of PGI2 (measured as 6-keto-PGF1 alpha) were degraded during one passage through the kidney. By infusing PGF2 at 8 nmol min-1 and PGI2 at 2 nmol min-1 renin release increased equally and the prostaglandin outputs increased to the same levels as during ureteral occlusion before indomethacin administration. ECA did not increase renin release after indomethacin administration. However, infusion of PGE2 during continuous ECA administration increased renin release in a dose-dependent manner similar to the experiments performed during ureteral occlusion. We conclude that PGI2 and PGE2 in the amounts synthesized in the kidney seem to be equally important stimulators of renin release but their relative potencies cannot be determined because the site of degradation is uncertain. Renin release is enhanced by intrarenal mechanisms activated by ECA infusion or ureteral occlusion, which both cause autoregulatory vasodilation and reduce NaCl reabsorption at the macula densa.