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

Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):410-5. doi: 10.1007/BF00178960.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelin-Converting Enzymes
  • Endothelins / administration & dosage
  • Endothelins / physiology*
  • Epoprostenol / metabolism*
  • Male
  • Metalloendopeptidases
  • Muscle, Smooth / metabolism*
  • Muscle, Smooth, Vascular / metabolism*
  • Protein Precursors / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism

Substances

  • Endothelins
  • Protein Precursors
  • 6-Ketoprostaglandin F1 alpha
  • Epoprostenol
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Endothelin-Converting Enzymes