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.
Pharmacology Department, Laboratori Guidotti SpA, San Piero a Grado, Pisa, Italy.
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D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000008:administration & dosage / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases; D009130:Muscle, Smooth / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011498:Protein Precursors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D016232:Endothelins; D011498:Protein Precursors; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes