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

FEBS Letters

Löffler, Bernd-Michael¹  Clozel, Martine¹  Breu, Volker¹ 

[1] Pharma Division, Preclinical Research, F.Hoffmann-La Roche Ltd., Grenzacher Strasse 124, CH-4002 Basel, Switzerland

关键词: Endothelin;    Endothelin receptor;    Endothelin receptor blockade;    Hypertension;   

DOI  :  10.1016/0014-5793(93)80384-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 ET_A and ET_B 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 ET_A 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 ET_B receptors.

【 授权许可】

Unknown