Münter K, Ehmke H, Kirchengast M
Preclinical Cardiology, Knoll, 67008 Ludwigshafen, Germany.
Am J Physiol. 1999 Mar;276(3):H1022-7. doi: 10.1152/ajpheart.1999.276.3.H1022.
The role of endothelin (ET)-1 in blood pressure homeostasis and the interaction with the renin-angiotensin system (RAS) was investigated in normotensive conscious dogs. ETA receptors were blocked by LU-135252 (1-30 mg/kg); trandolapril (2 mg/kg) or losartan (10 mg/kg) was used to inhibit the RAS. LU-135252 in oral doses of 3-30 mg/kg significantly reduced mean arterial pressure (MAP) by approximately 10 mmHg maximally, whereas trandolapril or losartan were without any effect. MAP reduction was more pronounced when LU-135252 was combined with either losartan (-15.5 +/- 3.2 mmHg; 2 h postadministration; P < 0.05) or trandolapril (-30.9 +/- 3.6 mmHg; P < 0.05). When endogenous nitric oxide (NO) generation was blocked but NO concomitantly infused, this synergistic effect on MAP was prevented. The data show that ET-1 contributes to the maintenance of blood pressure via ETA receptors. Furthermore, ET-1 and ANG II play a prominent role in the control of blood pressure by opposing the effects of NO. The pronounced blood pressure fall after combined blockade of ETA receptors and the RAS may be mediated by an enhanced release of NO.
在血压稳定状态下，研究了内皮素（ET）-1在血压稳态中的作用以及与肾素-血管紧张素系统（RAS）的相互作用。使用LU-135252（1-30毫克/千克）阻断ETA受体；使用群多普利（2毫克/千克）或氯沙坦（10毫克/千克）抑制RAS。口服剂量为3-30毫克/千克的LU-135252可使平均动脉压（MAP）最大降低约10毫米汞柱，而群多普利或氯沙坦则无任何作用。当LU-135252与氯沙坦（给药后2小时降低15.5±3.2毫米汞柱；P<0.05）或群多普利（降低30.9±3.6毫米汞柱；P<0.05）联合使用时，MAP降低更为明显。当内源性一氧化氮（NO）生成被阻断但同时注入NO时，对MAP的这种协同作用被阻止。数据表明，ET-1通过ETA受体有助于维持血压。此外，ET-1和血管紧张素II在通过对抗NO的作用来控制血压方面发挥着重要作用。ETA受体和RAS联合阻断后明显的血压下降可能是由NO释放增加介导的。
