A comparison of the effects of prostacyclin and 6-keto-prostaglandin E1 on renin release in the isolated rat and rabbit kidney.

Abstract A direct comparison of the relative potencies of the prostaglandins PGI 2 and 6-kto-PGE 1 to induce renin release was made in the isolated rat kidney, which was perfused with a synthetic medium at constant perfusion pressure. Both prostaglandins stimulated renin release in a dose-dependent manner (0.01 to 1 μM) and with equal potency. Also in the isolated rabbit kidney, PGI 2 and 6-keto-PGE 1 had the same potency to induce renin release at 1 μM final concentration. Following infusion of 6-keto-PGE 1 a small increase of vascular resistance in the rat kidney was observed, whereas in the rabbit kidney no constrictor effect was seen. When perfusate of PGI 2 or 6-keto-PGE 1 -infused rat kidneys were tested for antiaggregatory activity in the ADP induced aggregation of human platelets and compared with authentic standards, the results showed 6-keto-PGE 1 passes the kidney essentially unchanged, whereas only 25–40% of the infused PGI 2 appear in the venous perfusates, as judged from the recovery of antiaggregatory activity. Analysis of venous perfusates from 3 H-PGI 2 infused kidneys by high performance liquid chromatography indicates that about 25% of the infused PGI 2 remains intact, a major portion of the perfused radioactivity was identified as 6-keto-PGF 1α by combined gaschromatography-mass-spectrometry (19). We conclude that the renin-stimulating effect of PGI 2 is not secondary to its metabolism to 6-keto-PGE 1 , as has been suggested in the literature (8).