Endothelins induce prostacyclin release in both vascular and non-vascular tissue

The effects of an i.v. administration of endothelin-1, -2 and -3 (0.25-3 nmol kg-1) or their corresponding proendothelins (1-20 nmol kg-1) on blood pressure and 6 keto-prostaglandin F1 alpha (6 keto-PGF1 alpha) release in the anaesthetized ganglion-blocked rat were evaluated. The same peptides were tested for their ability to release 6 keto-PGF1 alpha from the rat vas deferens in vitro. Endothelins and proendothelins showed a transient hypotensive effect followed by a potent, long lasting vasopressor response. Blood pressure increase induced by endothelins was found to be dose-dependently correlated with 6 keto-PGF1 alpha plasma level increases. On the other hand proendothelins produced similar pressor responses, but their effect on 6 keto-PGF1 alpha plasma levels was much less intense at equipressor doses. The effects of endothelins on arterial pressure and 6 keto-PGF1 alpha release were phosphoramidon-insensitive, while the activities of proendothelins were reduced by phosphoramidon (10 mg kg-1 i.v.). Both endothelins (5-15 nmol/l) and proendothelins (100-300 nmol/l) were able to increase to a similar extent 6 keto-PGF1 alpha levels in the rat vas deferens incubation buffer. The releasing activity of endothelins was not modified by the pretreatment with phosphoramidon (50 mumol/l). This pretreatment strongly inhibited proendothelin-1 and -2 effects, but not that of proendothelin-3.