Clozel M, Breu V
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
FEBS Lett. 1996 Mar 25;383(1-2):42-5. doi: 10.1016/0014-5793(96)00212-8.
We used Ro 46-8443, non-peptidic antagonist selective of endothelin ETB receptors, to study the role of ETB receptors in rat hypertension models. In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats, it induced a pressor effect, due to blockade of ETB-mediated release of nitric oxide since L-NAME prevented it. In rats rendered hypertensive by chronic L-NAME, Ro 46-8443 did not induce a pressor but depressor effect. Thus, in DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ETB receptors, while in normotensive rats the prevailing role of ETB receptors seems to be in mediating a vasoconstrictor tone.
我们使用了Ro 46-8443（一种内皮素ETB受体选择性非肽类拮抗剂）来研究ETB受体在大鼠高血压模型中的作用。在正常血压大鼠中，Ro 46-8443可降低血压，但在自发性高血压大鼠（SHR）和去氧皮质酮（DOCA）大鼠中，由于L- NAME可阻止其作用，Ro 46-8443因阻断ETB介导的一氧化氮释放而诱导升压效应。在慢性L- NAME致高血压大鼠中，Ro 46-8443未诱导升压而是降压效应。因此，在DOCA大鼠和SHR中，Ro 46-8443显示出内皮“血管舒张”ETB受体的主要影响，而在正常血压大鼠中，ETB受体的主要作用似乎是介导血管收缩张力。
