Low-dose endothelin stimulates release of prostaglandin I2 from isolated perfused hind legs in the rat.

A direct measurement of 6-keto-prostaglandin F1a (6-keto-PGF1a), a stable metabolite of prostaglandin I2, was made in the perfusate from isolated rat hind legs perfused with Krebs-Ringer solution. The rate of release of 6-keto-PGF1a was 5.28 +/- 0.24 ng during the first perfusion period of two min, and it remained stable at least for 40 min. The biological integrity of the preparation was confirmed by inhibition (52%) of 6-keto-PGF1a release by indomethacin (5 X 10(-5) M) in the perfusion medium. Low-dose infusion (5, 10, and 20 pM, for 10 min each) of endothelin (ET) elicited small but significant increment in the release of 6-keto-PGF1a in a dose-dependent fashion; the maximal per cent increase of 6-keto-PGF1a release evoked by ET (20 pM) was approximately +40% over the basal rate. These results taken together with the previous observations of synthesis of ET in the vascular tissue suggest an intriguing relationship between vasoconstrictive ET and vasodilatory prostaglandins in the local control of vascular tone.