Stimulation of renin release by 6-oxo-prostaglandin E1 and prostacyclin

Abstract

1 Renin release induced by 6-oxo-prostaglandin E1 (6-oxo-PGE1) was compared to release in response to prostacyclin (PGI2) and 6-oxo-PGF1 alpha in slices of rabbit renal cortex. 2 Krebs-Ringer medium bathing slices of renal cortex was collected for renin assay after four successive 20 min intervals (periods I-IV). Renin release did not increase during periods I to IV in untreated slices. Agonists were added, only once, at the beginning of period III. Between periods III and IV, the incubation solution was aspirated and replaced with fresh medium. 3 PGI2 increased renin release during period III while 6-oxo-PGE1 stimulated release during periods III and IV. 6-oxo-PGE1 stimulated renin release (24%-74%) in concentrations ranging from 1-33 microM while PGI2 stimulated release at 10 microM (60%) but not at 5 microM. 6-oxo-PGF1 alpha, 10 microM, did not release renin during period III (period III, 9%), but caused a small rise in period IV (29%). 4 6-oxo-PGE1, unlike PGI2, was stable under the incubation conditions (pH 7.4, 37 degrees C) as indicated by recovery of undiminished platelet anti-aggregatory material after 20 min. 5 In the rabbit kidney, activity of 9-hydroxyprostaglandin dehydrogenase was greatest in the cortex and negligible in the papilla, corresponding to the zonal distribution of renin. 6 The prominent and sustained in vitro renin releasing effect of 6-oxo-PGE1, as well as the cortical localization of enzyme activity capable of generating this stable prostacyclin metabolite, suggest that formation of 6-oxo-PGE1 may contribute to PGI2-induced renin release and may explain the delayed stimulation caused by 6-oxo-PGF1 alpha.