Effect of different endothelin receptor antagonists and of the novel non-peptide antagonist Ro 46-2005 on endothelin levels in rat plasma

FEBS Lett. 1993 Oct 25;333(1-2):108-10. doi: 10.1016/0014-5793(93)80384-7.


The goal of our study was to evaluate and compare the effects of receptor blockade with different endothelin (ET) receptor antagonists on plasma concentrations of ET-1, big ET-1 and ET-3 in conscious rats. Ro 46-2005 10 mg/kg, i.v.), a novel non-peptide antagonist of both ETA and ETB receptors, increased the concentrations of ET-1 in plasma to 200 +/- 13% of basal levels (P < 0.001). This effect was dose- and time-dependent and reached a maximum at 15 min. Ro 46-2005 had no effect on plasma concentrations of big ET-1 and only a minor effect on those of ET-3. In contrast to Ro 46-2005, the selective peptide ETA antagonists BQ-123 and FR-139317 had no effect on plasma ET-1 concentrations. The increase in plasma ET-1 concentrations by Ro 46-2005 was most likely not due to de novo synthesis, since big ET-1 levels were not increased and peak levels were reached early after compound injection, but perhaps to displacement of ET-1 from the ETB receptors.

MeSH terms

  • Animals
  • Endothelin Receptor Antagonists*
  • Endothelins / blood*
  • Kinetics
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology*


  • Endothelin Receptor Antagonists
  • Endothelins
  • Pyrimidines
  • Sulfonamides
  • Ro 46-2005